Glucagon
Author(s)
Bibliographic Information
Glucagon
(Handbook of experimental pharmacology, v. 66,
Springer-Verlag, 1983-
- part 1 : us
- part 2 : us
- part 1 : gw
- part 2 : gw
- 3
Available at / 47 libraries
-
Habikino Health Sciences Library,Osaka Prefecture University
part 2 : us20950276771,
part 1 : us20950276763 -
Osaka University, Main Library
314100093211,
V.66?PT.1???????08703142128, V.66?PT.2???????08703142136 -
part 1 : gwQV/34/Han1210015738,
part 2 : gwQV/34/Han1210015804, 3QV/34/Han1210018642 -
pt. 1QV34||H236||v.66(1)27186,
pt. 2QV34||H236||v.66(2)27187, 3QV34||H236||v.12336814 -
part 1 : gw491.5||H,29||(66)1||58-914530003413,
part 2 : gw491.5||H,29||(66)2||58-948230003414, 3491.5||H,29||(123)||08-1542230004953 -
part 1 : Germany491.508||Ha 14||1-66-1108996,
part 2 : Germany491.508||Ha 14||1-66-2108995 -
埼玉医科大学 附属図書館埼医大図
3QV34/H/123000084939,
part 1 : gwQV34/H/66/1000746271, part 2 : gwQV34/H/66/2000746305 -
Saga University Medical Library
part 1 : gwQV5||H 29||66-12187003525,
part 2 : gwQV5||H 29||66-22187003536 -
Medical Library, The University of Tokyo図書
part 1 : gwQV:34:ha4300006287,
part 2 : gwQV:34:ha4300006295, part 3QV:34:HA4310560919 -
part 1 : gwM1.508||H||66-1 (R6179)1120017931,
part 2 : gwM1.508||H||66-2 (R6180)1120017942 -
part 1 : gw491.5||H29||66-1118302183,
part 2 : gw491.5||H29||66-2118302761, 3491.5||Ha||123119600287 -
University of Toyama Library, Medical and Pharmaceutical Library図
part 1 : usQV4//H236h//V66-1T9500002788*,
part 2 : usQV4//H236h//V66-2T9500002789*, 3QV4||H236H||V.12395000158033 -
part 1 : gw491.5||H||66(1)40807122,
part 2 : gw491.5||H||66(2)40812133, 3491.5||H41175207 -
part 1 : gw499.208||H29||66-111042244,
part 2 : gw499.208||H29||66-211042245, 3499.208||H29||12311042302 -
part 1 : gwQV||5||66/187101700,
part 2 : gwQV||5||66/287101701, 3QV||5||12396200705,0000962007054 -
No Libraries matched.
- Remove all filters.
Note
Includes bibliographies and index
Description and Table of Contents
- Volume
-
part 1 : gw ISBN 9783540120681
Description
Table of Contents
- Chemistry and Physicochemistry of Glucagon.- 1 Chemical Characteristics of Glucagon.- A. Introduction.- B. Isolation and Purification.- C. Properties.- D. Amino Acid Sequence.- E. Covalent Chemical Modification and Biologic Function.- I. Limitations of the Approach.- II. General Considerations.- III. The Question of Several Active Sites.- IV. Amino Terminal and Diamino Modifications.- V. Inhibitors of Glucagon.- VI. Modifications of Glutamyl, Lysyl, Arginyl, and Tryptophyl Residues.- VII. Modifications of Tyrosyl Residues.- VIII. Methionyl Residue and Carboxyl Terminal Modifications.- IX. Summary of Covalent Modifications and Function.- References.- 2 The Chemical Synthesis of Glucagon.- A. Introduction.- B. Early Synthetic Efforts.- C. The First Total Synthesis.- D. Further Syntheses by Fragment Condensation in Solution.- E. Solid Phase Fragment Synthesis.- F. Stepwise Solid Phase Synthesis.- G. Conclusions.- References.- 3 The Conformation of Glucagon.- A. Introduction.- B. The Crystal Structure.- I. Crystals.- II. Protomer Conformation.- III. Trimer Conformation.- C. The Solution Structure.- I. Monomer.- II. Trimers.- III. Fibrils.- D. Conformation of Micelle-Bound Glucagon.- E. Conformation and Storage Granules.- F. Conformation and Receptor Binding.- References.- Morphology of the A-cell of Islets of Langerhans, Biosynthesis of Glucagon and Related Peptides.- 4 Glucagon- and Glicentin-Producing Cells.- A. Introduction.- B. Pancreas.- I. Morphological Features.- II. Distribution of A-cells.- III. Intracellular Distribution of Secretory Polypeptides.- C. Digestive Tract.- D. Pathology of A- and L-cells.- E. Conclusions.- F. Appendix.- I. Sampling of the Pancreas.- II. Immunofluorescence Technique.- III. Quantitative Evaluation.- References.- 5 Ontogeny and Phylogeny of the Glucagon Cell.- A. Introduction.- B. Material, Methods, Nomenclature.- C. Prokaryotes, Eukaryote Protozoa, Coelenterates.- D. Protostomian Invertebrates.- I. Molluscs.- II. Arthropods.- 1. Crustaceans.- 2. Insects.- E. Deuterostomian Invertebrates.- I. Echinoderms, Hemichordates.- II. Protochordates (Tunicates, Amphioxus).- F. Vertebrates.- I. Agnatha (Cyclostomes
- Jawless Fish).- II. Gnathostomata.- 1. Cartilaginous Fish.- 2. Bony Fish.- 3. Tetrapods.- G. Discussion and Summarising Conclusions.- References.- 6 The Biosynthesis of Glucagon.- A. Introduction.- B. General Aspects of the Formation, Intracellular Conversion, and Storage of Peptide Hormones.- C. Biosynthesis of Glucagon.- I. Formation of Preproglucagon.- II. Formation and Conversion of Proglucagon.- III. Structure and Storage of Proglucagon and Glucagon.- D. Concluding Remarks.- References.- 7 Glucagon, Glicentin, and Related Peptides.- A. Introduction.- B. The Immunochemistry of Gut GLIs.- C. The Chemistry of Crude Gut GLIs.- I. Distribution.- II. Size.- III. Charge.- D. The Chemistry of Glicentin, GRPP, and Oxyntomodulin.- I. Isolation of Glicentin.- II. Sequence of Glicentin.- III. Relationship of Glicentin to Other Peptides.- IV. Structural Analysis of Glicentin.- V. Isolation of GRPP.- VI. Chemistry of GRPP.- VII. Relationship of GRPP to other Peptides.- VIII. Chemistry of Oxyntomodulin.- E. The Immunochemistry of Glicentin.- I. Reaction of Glicentin with Anti-Glucagon Sera.- II. Anti-Glicentin Sera.- III. Radioimmunoassay for Glicentin.- IV. Distribution of Immunoreactive Glicentin.- F. Glicentin Cells.- I. Intestinal Gut GLI Cells.- II. The Glicentin Cell.- 1. Animal Tissue.- 2. Normal Human Tissue.- 3. Pathologic Human Tissue.- III. Fine Structure of the A- and L-cell Secretory Granules.- G. Glicentin and Glucagon Biosynthesis.- H. Circulating Gut GLIs.- I. Radioimmunoassay of Gut GLI.- II. Factors Controlling Gut GLI Release.- III. Circulating Forms of Gut GLI.- IV. Circulating Gut GLI Levels in Adult Humans.- V. Circulating Gut GLI Levels in the Perinatal Period.- J. Effects of Gut GLIs.- I. Postulated Effects.- II. Effects of Partially Purified Gut GLIs.- III. Effects of Pure Gut GLIs.- 1. Synthetic Peptides.- 2. Oxyntomodulin.- 3. Glicentin.- K. Discussion.- I. Clinical Significance of Circulating Gut GLIs.- II. Structure-Function Relationships of Gut GLIs.- III. Role of Gut GLIs.- References.- Production and Assay of Glucagon.- 8 Glucagon Preparations.- A. Introduction.- B. Production.- C. Pharmaceutical Preparations.- D. Assays.- I. Physicochemical Methods.- 1. Ultraviolet Absorption.- 2. Electrophoretic Methods.- 3. Chromatographic Methods.- 4. High Pressure Liquid Chromatography.- II. Bioassay Methods.- B. Stability.- C. Timing of Action.- References.- 9 The Immunogenicity of Glucagon.- A. Introduction.- B. Immunogenicity of Glucagon and Glucagon Fragments.- I. Species Used for Immunization.- II. Immunogen.- 1. Glucagon.- 2. Glucagon Fragments.- 3. Coupling Procedures.- 4. Mode of Administration, Dose, Frequency, Adjuvant.- C. Characterization of the Glucagon Antibodies.- I. Affinity and Capacity.- II. Specificity.- 1. Reactivity with Glicentin, Gut GLIs, and Glucagon Analogs.- 2. Reactivity with Glucagon Fragments.- D. Purification of Mixtures of Glucagon Antibodies.- E. Summary.- I. Production of COOH-Terminal Specific Antibodies.- II. Production of NH2-Terminal Specific Antibodies Giving Linear Dilution Curves with Gut GLI.- References.- 10 Immunoassays for Glucagon.- A. Introduction.- B. Method of Radioimmunoassay.- I. Sources of Peptides.- II. Preparation and Purification of Radiolabeled Ligand.- III. Preparation of Standard.- IV. Production and Characterization of Antisera.- 1. Antigenic Determinants and Coupling Procedures.- 2. Immunization Procedure.- 3. Characterization of Antisera.- V. Assay Procedure.- C. Measurement of Glucagon-Related Peptides.- I. Collection and Processing of Plasma.- II. Contribution of Different Species to Plasma Levels.- D. Summary.- References.- 11 Heterogeneity of Circulating Glucagon and Glucagon-Like Immunoreactivity.- A. Introduction.- B. Types of Glucagon Antibodies.- I. COOH Terminal-Specific..- II. NH2 Terminal-Specific.- C. Plasma COOH Terminal-Specific Antibody-Reacting Components...- I. Plasma IRG Components in the Normal Adult.- 1. Basal State.- 2. After Intravenous Arginine Administration.- 3. After Glucose Administration.- II. Plasma IRG Components in the Neonatal Period.- III.Plasma IRG in Pathologic States.- 1. Glucagonoma.- 2. Diabetes.- 3. Pancreatectomy.- 4. Chronic Hypoglycemia.- 5. Renal Failure.- 6. Cirrhosis of the Liver.- 7. Other Conditions.- IV. Origin of Plasma IRG Components.- D. Plasma GLI Components.- I. Basal State and During Glucose Absorption.- 1. Normal Humans.- 2. Normal Dogs.- 3. Nephrectomized Dogs.- II. Origin of Plasma GLI Components.- E. Concluding Remarks.- References.- 12 Radioreceptorassays for Glucagon.- A. Introduction.- B. Glucagon Radioreceptorassay Methodology.- I. Receptor Preparations.- 1. Isolated Cells.- 2. Isolated Membranes.- II. Radioactive Glucagon.- III. Incubation Conditions.- 1. Temperature and Incubation Time.- 2. Reagent Volumes.- 3. Assay Buffer.- 4. Degradation.- 5. Plasma Effects.- 6. Separation.- C. Performance and Applications of the Glucagon Radioreceptorassay.- I. Requirements for Ligand-Receptor Interaction.- 1. Coupling of Binding to Biologic Activity.- 2. Specificity of the Receptor.- II. Applications.- 1. Assay of Gut Peptides.- 2. Assay of Pancreatic Peptides.- 3. Glucagonomas.- References.- Actions of Glucagon.- 13 The Actions of Glucagon at Its Receptor: Regulation of Adenylate Cyclase.- A. Introduction.- B. Characteristics of Hormone-Sensitive Adenylate Cyclase Systems.- I. Role of GTP in Hormone Action.- II. Specificity for Guanine Nucleotides.- III. Effects of Adenosine.- IV. Role of GTPase.- V. Actions of Cholera Toxin.- VI. Actions of Guanine Nucleotides on Hormone Receptors...- VII. Effects of GTP on Hormone Binding Versus Action.- VIII. Multiple Sites of GTP Action.- IX. Characteristics of the N Unit.- X. Independent Complexes of N with R and C.- XI. Characteristics of the Catalytic Unit.- XII. Regulation by Divalent Cations.- XIII. The Role of Sulfhydryl Groups in Transduction.- XIV. The Role of Membrane Lipids.- XV. Desensitization of Glucagon Action.- XVI. Relationship Between Glucagon Binding and Action.- C. The Glucagon Receptor.- D. Target Analysis of the Glucagon-Sensitive Adenylate Cyclase System.- E. A Model for Glucagon Action.- F. The Glucagon "Message".- G. Summary and Conclusions.- References.- 14 Glucagon and Liver Glycogen Metabolism.- A. Glucagon, Glycogenolysis, and Glucose Output.- B. The Enzymes Involved in Hepatic Glycogen Metabolism.- I. The General Pathways.- II. The Regulated Enzymes.- 1. Protein Kinases.- 2. Protein Phosphatases.- B. The Enzymic Mechanism of Glucagon Action.- I. Glucagon Causes Glycogenolysis via Phosphorylase a.- 1. Facts.- 2. Questions.- II. Glycogenolysis Mediated by cAMP.- 1. Activation of the Glycogenolytic Cascade.- 2. An Effect of cAMP on Phosphorylase Phosphatase.- III. Can Glucagon Act in a cAMP-Independent Way?.- IV. Glucagon also Causes Inactivation of Glycogen Synthase.- D. Expression and Modulation of Glucagon Action.- I. Regulation of Hepatic Glycogen Metabolism by Glucagon.- II. Modulation of the Response to Glucagon.- 1. Effects of Insulin and Glucose.- 2. Glucocorticoid Hormones.- References.- 15 Glucagon and Gluconeogenesis.- A. Introduction.- B. Sites of Action of Glucagon on Hepatic Gluconeogenesis.- I. Action on Mitochondrial Sites.- 1. Pyruvate Carboxylase.- 2. Pyruvate Dehydrogenase.- II. Action on Extramitochondrial Sites.- 1. Phosphoenolpyruvate-Pyruvate Substrate Cycle.- 2. Fructose-6-phosphate-Fructose-l,6-bisphosphate Substrate Cycle 333 III. Other Possible Sites of Glucagon Action.- C.Summary and Overview.- References.- 16 Glucagon and Liver Glucose Output In Vivo.- A. Introduction.- B. Effects of Glucagon on Hepatic Glucose Production.- I. Glycogenolysis.- II. Gluconeogenesis.- C. Glucagon-Insulin Interaction in the Regulation of Hepatic Glucose Production.- I. Glycogenolysis.- II. Gluconeogenesis.- D. Role of Glucagon in the Regulation of Glucose Homeostasis.- I. Feasting.- II. Fasting.- III. Exercise.- IV. Diabetes Mellitus.- References.- 17 Glucagon and Ketogenesis.- A. Introduction.- B. Intrahepatic Factors in the Regulation of Ketogenesis.- C. Emergence of a Ketogenic Role for Glucagon.- I. Studies in Animals.- II. Studies in Humans.- D. Interactions of Insulin and Glucagon on Hepatic Metabolism...- I. The "Fed to Fasted" Transition.- II. The "Fasted to Fed" Transition.- E. Overview.- References.- 18 Glucagon and Amino Acid Metabolism.- A. Introduction.- B. Effects of Glucagon on Amino Acid Levels.- C. Glucagon and Liver Amino Acid Metabolism.- D. Glucagon and Muscle Amino Acid Metabolism.- E. Physiologic and Pathologic States in Which Glucagon Affects Amino Acid Metabolism.- I. Glucagon Deficiency.- II. Glucagon Excess.- 1. Diabetes Mellitus.- 2. Glucagonoma.- 3. Trauma and Sepsis.- F. Summary.- References.- 19 Glucagon and Adipose Tissue Lipolysis.- A. Introduction.- B. Glucagon and Adipose Tissue.- I. Species Variations in Glucagon-Induced Lipolysis.- II. Mechanisms Involved in the Lipolytic Action of Glucagon...- II. Glucagon-Induced Lipolysis and Glucose Metabolism in the Adipocyte.- III. Factors Affecting Glucagon-Induced Adipose Tissue Lipolysis...- 1. Size of the Adipocytes, Age and Nutritional Status of the Animals.- 2. Innervation of the Adipose Tissue.- 3. Hypophysectomy, Adrenalectomy, Hypothyroidism.- 4. Insulin.- 5. Prostaglandins and Prostaglandin Synthesis Inhibitors...- 6. Other Factors.- V. Glucagon-Like Peptides and Adipose Tissue Lipolysis.- VI. Brown Adipose Tissue and Nonshivering Thermogenesis...- VII. Adipose Tissue Lipoprotein Lipase Activity.- C. Glucagon and Circulating Free Fatty Acids.- I. Intravenous, Subcutaneous, or Intramuscular Injection of High Doses of Glucagon in Mammals.- 1. The Early Rise in Plasma FFA.- 2. The Secondary Drop in Plasma FFA.- 3. The Late Increase in Plasma FFA.- II. Intraarterial, Intravenous, or Intraportal Infusion of Low Doses of Glucagon in Mammals.- III. Intravenous Injection or Infusion of Glucagon in Birds.- D. Physiologic Importance of Glucagon-Induced Lipolysis.- I. Fasting.- II. Muscular Exercise.- III. Adaptation to Extrauterine Life.- References.- 20 Glucagon and Lipoprotein Metabolism.- A. Introduction.- B. Glucagon Effects on Liver Lipid Metabolism.- C. Metabolic Effects of Glucagon In Vivo.- References.- 21 Glucagon and Liver Regeneration.- A. Nature of Liver Regeneration.- I. Phenomenology.- 1. Key Questions.- 2. Background.- 3. Kinetic Aspects.- II. The Endocrine Hypothesis.- 1. Concerted Control by Peptide Hormones.- 2. Interactions with Nutrients.- 3. Two Sequential Rate-Limiting Events.- B. Regulatory Evidence.- I. Direct.- II. Indirect.- C. Physiology.- I. Extrahepatic.- 1. Bloodstream.- 2. Responsive Tissues.- II. Hepatic.- 1. Hepatocytes.- 2. Nonparenchymal Cells.- III. Specificity.- 1. Mimetics.- 2. Nonhepatocyte Targets.- D. Mechanisms of Action.- I. Potentiation of Signal 2.- 1. Kinetic Evidence.- 2. Synergisms with Other Peptide Hormones.- 3. Nonrequirement of Glucocorticoids.- II. Molecular.- 1. cAMP-Dependent.- 2. cAMP-Independent.- III. Functional Linkages.- 1. Na+ Gradient-Dependent Amino Acid Cotransport.- 2. Altered Hepatocyte Lipid Metabolism.- 3. Deoxyribonucleoside Triphosphate Production.- IV. Inhibitory Aspects.- 1. Hepatocyte Loci.- 2. Desynchronization of Diurnal Rhythms.- E. Future Goals.- I. Role of Other Factors.- 1. High Molecular Weight Glucagon.- 2. Intrahepatic Loci.- II. Additional Problems.- 1. Complexity of Animal Cell Regulatory Processes.- 2. Limitations of Current Experimental Models.- III. Reasons for Optimism.- F. Summary.- References.- 22 Glucagon and Insulin Secretion.- A. Introduction and Historical Overview.- B. Experimental Stimulation of Insulin Secretion by Glucagon in Vivo and In Vitro.- I. Effect of Food and Fasting.- II. Adrenergic Effects.- III. Insulinotropic Effect of Glucagon in Disease.- IV. Insulinotropic Effect of Glucagon in the Child, Neonate, and Fetus.- V. Mechanism of Insulinotropic Effect of Glucagon.- C. Consideration of the Evidence for the Endogenous Insulinotropic Effect of Glucagon.- I. Inherent Difficulties in Testing the Hypothesis.- II. Anatomy of the Islets of Langerhans.- III. Dynamic and Magnitudinal Changes in Glucagon and Insulin After Secretagogue Administration.- IV. Augmentation of Insulin Secretion by Protein and/or Fat Meals. 497 V. Active and Passive Immunization.- VI. Diabetes Mellitus.- VII. Glucagonoma-Induced Hyperglucagonemia and Hyperinsulinemia 498 VIII. Evidence Against an Insulinotropic Effect of Endogenous Glucagon.- D. Potential Physiologic and Pathologic Significance of the Insulinotropic Effect of Glucagon.- E. Effect of Insulin on Glucagon Secretion.- I. Effect of Exogenous Insulin on Glucagon Release in Vivo.- II.Effect of endogenous Insulin on Glucagon Release in Vivo.- III. Effect of Exogenous Insulin on Glucagon Secretion in Vitro.- IV. Mechanism of the Glucagonsuppressive Effect of Insulin.- F. Evidence For and Against an Intraislet Negative Insulin-Glucagon Feedback.- G. New Hypotheses and Concepts in Local Intraislet Regulation of A- and B-cells.- I. Compartmentalization: Systemic Versus Local Intraislet Effects.- II. The Principle of Uncertainty in Studies of Local Islet Interactions.- III. Possible Paracrine Effects on Growth and Differentiation.- H. Synopsis and Conclusions.- References.
- Volume
-
part 2 : gw ISBN 9783540122722
Table of Contents
- Control of Glucagon Secretion.- 23 Glucose in the Control of Glucagon Secretion.- A. Introduction.- B. Effect of Changes in Extracellular Glucose Concentration on Glucagon Secretion.- I. Increases in Extracellular Glucose Concentration.- 1. In Vivo Studies.- 2. In Vitro Studies.- II. Decreases in Extracellular Glucose Concentration.- 1. In Vivo Studies.- 2. In Vitro Studies.- C. Mechanism of Glucose Action on A-cell Function.- I. A-cell Glucose Metabolism.- II. Effects of Glucose Metabolites and Inhibitors of Glucose Metabolism.- III. Evidence for a Glucoreceptor Mechanism not Involving Metabolism.- IV. Calcium-Potassium and Glucose Action.- V. Mechanism for A-cell Response to Hypoglycemia.- 1. General Considerations.- 2. Sympathetic and Parasympathetic Modulation.- D. Modulatory Effects of Glucose on A-cell Function.- I. Acute Effects.- II. Prolonged and Chronic Effects.- References.- 24 The Amino Acid-Induced Secretion of Glucagon.- A. Introduction.- B. Phenomenology.- I. In Vitro.- 1. Isolated Perfused Pancreas.- 2. Pancreatic Fragments, Islets and Islet Cells.- 3. Gastric A-cells In Vitro.- 4. Other Tissues.- II. In Vivo.- 1. Human Studies.- 2. Studies in Normal Dogs.- 3. Other Studies.- C. Mechanism of Amino Acid-Induced Glucagon Release.- I. Contribution of the Microtubular-Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Potassium and Glucose Action.- V. Mechanism for A-cell Response to Hypoglycemia.- 1. General Considerations.- 2. Sympathetic and Parasympathetic Modulation.- D. Modulatory Effects of Glucose on A-cell Function.- I. Acute Effects.- II. Prolonged and Chronic Effects.- References.- 24 The Amino Acid-Induced Secretion of Glucagon.- A. Introduction.- B. Phenomenology.- I. In Vitro.- 1. Isolated Perfused Pancreas.- 2. Pancreatic Fragments, Islets and Islet Cells.- 3. Gastric A-cells In Vitro.- 4. Other Tissues.- II. In Vivo.- 1. Human Studies.- 2. Studies in Normal Dogs.- 3. Other Studies.- C. Mechanism of Amino Acid-Induced Glucagon Release.- I. Contribution of the Microtubular-Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Potassium Pump.- IV. Ammonium.- E. Anions.- F. Conclusions.- References.- 27 Cyclic Nucleotides in the Control of Glucagon Secretion.- A. Introduction.- B. Effects of Exogenous Cyclic AMP.- C. Effects of Phosphodiesterase Inhibitors.- D. Effects of Agents Thought to Act via Endogenous Cyclic AMP.- E. Conclusions..- References.- 28 Prostaglandins and Glucagon Secretion.- A. Introduction.- I. Origin and Metabolism of Prostaglandins.- II. Prostaglandins as Local or Intracellular Messengers.- III. Methodological Considerations.- B. Studies In Vitro on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- II. Role of Endogenous Prostaglandins.- 1. Prostaglandin Biosynthesis by Islet Tissue.- 2. Endogenous Prostaglandins and Glucagon Secretion In Vitro.- C. Studies In Vivo on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- 1. Rats.- 2. Dogs.- 3. Humans.- II. Role of Endogenous Prostaglandins.- D. Summary and Conclusions.- References.- 29 Hormones in the Control of Glucagon Secretion.- A. Introduction.- B. Thyroid Hormones.- C. Calcium-Regulating Hormones.- I. Parathyroid Hormone.- II. Calcitonin.- III. Vitamin D.- D. Steroid Hormones.- I. Glucocorticoids.- II. Mineralocorticoids.- III. Sex Steroids.- E. Placental Hormones.- F. Gastrointestinal Hormones.- I. Gastric Inhibitory Polypeptide.- II. Vasoactive Intestinal Peptide.- III. Secretin.- IV. Porcine Intestinal Heptacosapeptide.- V. Bombesin.- VI. Cholecystokinin.- VII. Gastrin.- VIII. Cerulein.- IX. Motilin.- G. Pituitary Hormones.- I. Growth Hormone.- II. Adrenocorticotropic Hormone.- III. Endorphins and Enkephalins.- H. Hypothalamic Hormones.- I. Hypothalamic Lesions.- II. Substance P and Neurotensin.- III. Unidentified Polypeptides.- J. Conclusions.- References.- 30 Neural Control of Glucagon Secretion.- A. Introduction.- B. Anatomic Observations.- I. Neural Pathways.- II. Species Variations.- C. Experimental Observations.- I. Central Nervous System Studies.- II. Nerve Stimulation and Sectioning Studies.- III. Infusion Studies.- D. Physiologic and Pathophysiologic Observations.- E. Neural Control of Gastric Glucagon.- F. Conclusions.- References.- 31 Intraislet Insulin-Glucagon-Somatostatin Relationships.- A. Introduction.- B. Overview of Islet Anatomy.- C. General Mechanisms of Communication Between Cells.- D. Potential Interactions Within Islets.- I. Potential Interactions Between Cells.- 1. Basic Scheme.- 2. Effect of Glucagon Upon B- and D-cells.- 3. Effect of Somatostatin Upon A- und B-cells.- 4. Effect of Insulin Upon A- and D-cells.- 5. Pancreatic Polypeptide as an Ignored Entity and Why.- 6. Other Potential Islet Mediators.- II. Neural Control.- 1. Cholinergic Agonism.- 2. Adrenergic Agonism.- 3. Local Presynaptic Autonomic Regulation.- 4. Peptidergic and Purinergic Regulation.- III. Potential Role of Gap Junctions as Determinants of Coordination Between Islet Cells.- E. Anatomic Determinants of Islet Regulation.- F. Indirect Experimental Evidence for Interaction Between Islet Cells.- G. Efforts to Demonstrate Local Interactions Directly with Immune Neutralization.- H. Arguments Against Islet Interactions.- J. Oscillation of Secretion Suggesting Coordination Between Islets.- K. Consideration of an Islet-Acinar Portal System.- L. Islet Interrelationships in Diabetes.- M. Overview and Conclusions.- References.- 32 Pharmacologic Compounds Affecting Glucagon Secretion.- A. Introduction.- B. Drugs Used in the Treatment of Diabetes.- I. Insulin.- II. Sulfonylureas.- III. Biguanides.- C. Drugs Related to the Cholinergic System.- D. Drugs Related to the Sympathetic Nervous System.- I. Reserpine.- II. Beta-Adrenergic Blocking Agents.- III. Alpha-Adrenergic Blocking Agents.- IV. Clonidine.- V. L-Dopa, Dopamine, and Bromocriptine.- VI. Diazoxide and Tolmesoxide.- E. Serotonin and Serotonin Antagonists.- F. Drugs Affecting Ionic Concentrations and/or Fluxes.- I. Calcium, Calcitonin, and Vitamin D.- II. Verapamil and Procaine.- III. Veratridine, Ouabain, and Hydroquinidine.- G. Drugs Affecting Lipid Metabolism.- H. Drugs Acting on the Central Nervous System.- I. Diphenylhydantoin, Diazepam, and Haloperidol.- II. Morphine, Endorphins, and Enkephalins.- J. Hormonal Steroids.- I. Glucocorticoids.- II. Contraceptive Steroids.- K. Drugs Affecting the Mitotic Spindle.- L. Somatostatin and Somatostatin Analogs.- References.- Extrapancreatic Glucagon.- 33 Extrapancreatic Glucagon and Its Regulation.- A. Introduction.- B. Extrapancreatic Glucagon in the Canine Stomach.- I. Presence of A-cells.- II. Presence of Glucagon.- III. Control of Gastric Glucagon Release In Vitro.- 1. Role of Glucose and Insulin.- 2. Stimulation by Arginine.- 3. Role of the Autonomic Nervous System.- 4. Possible Role of Prostaglandins.- IV. Secretion of Gastric Glucagon In Vivo.- V. Physiologic and Pathophysiologic Relevance of Extrapancreatic Glucagon.- C. Gastrointestinal Glucagon in Other Animal Species.- D. Glucagon and the Salivary Glands.- E. Other Extrapancreatic Localizations of Glucagon.- F. In Vivo Generation of Glucagon from Glucagon-Like Immunoreactive Peptides.- G. Extrapancreatic Glucagon in Humans.- H. Conclusions.- References.- Glucagon in Various Physiological Conditions.- 34 Glucagon and Starvation.- A. Introduction.- B. The Postabsorptive State.- C. Glucoregulatory Hormones in Starvation.- D. Metabolic Alterations in Starvation.- I. The Early Phase.- II. Prolonged Starvation.- E. Summary and Conclusions.- References.- 35 Glucagon and Pregnancy.- A. Introduction.- I. Impaired Glucose Tolerance in Pregnancy.- II. Metabolic Adaptations to Pregnancy.- B. Plasma Glucagon in the Fasted State.- I. Changes After Overnight Fasting.- II. Changes After Prolonged Fasting and Insulin-Induced Hypoglycemia.- III. Placental Transfer of Glucagon and Morphology of A-cells in Pregnancy.- C. Plasma Glucagon in the Fed State.- I. Response to Glucose Administration.- II. Response to Amino Acids.- III. Response to Mixed Meals.- D. Summary and Conclusions.- References.- 36 Glucagon in the Fetus and the Newborn.- A. Introduction.- B. Ontogenesis of Glucagon in Pancreas and Plasma.- I. Rat.- II. Rabbit.- III. Sheep.- IV. Human.- C. Glucagon Secretion in the Fetus.- I. Impermeability of the Placenta to Glucagon.- II. Control of Glucagon Secretion in the Fetus.- 1. Changes in Glucose Concentration.- 2. Effects of Amino Acids.- 3. Effects of Neurotransmitters.- 4. Effects of Hypoxia.- 5. Prolonged Pregnancy.- D. Glucagon Secretion in the Newborn.- I. Evidence for a Role of the Sympathetic Nervous System in the Neonatal Surge of Glucagon.- II. Glucagon Secretion in Newborn Infants of Diabetic Mothers.- III. Glucagon Secretion During the Suckling Period.- IV. Glucagon Secretion During the Weaning Period.- E. Metabolic Effects of Glucagon.- I. In the Fetus.- II. In the Neonate.- III. During the Suckling Period.- IV. During the Weaning Period.- F. Glucagon Receptors in the Perinatal Period.- References.- 37 Glucagon as a Counterregulatory Hormone.- A. Glucose Counterregulation, an Overview.- B. Glucagon in the Prevention of Hypoglycemia.- I. The Postabsorptive State.- II. The Intraprandial State.- C. Glucagon in the Restoration of Normoglycemia.- D. Glucagon and the Somoygi Phenomenon.- E. Summary.- References.- 38 Glucagon and Its Relationship to Other Glucoregulatory Hormones in Exercise and Stress in Normal and Diabetic Subjects.- A. Introduction.- B. Exercise.- I. Metabolic Events During Exercise.- II. Fuel Sources During Exercise.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Changes During Exercise.- IV. Hormonal Interactions in the Control of Glucoregulation During Exercise.- 1. Role of Insulin.- 2. Role of Catecholamines.- 3. Role of Glucagon.- V. The Response to Exercise in Diabetic Subjects.- 1. Exercise in Insulin-Dependent Diabetics.- 2. Exercise in Noninsulin-Dependent Diabetics.- C. Stress.- I. Hormonal Response to Stress.- II. Major Changes in Fuels or Energy Substrate During Stress.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Interactions in Glucoregulation During Stress.- 1. Pathologic Stress States.- 2. Experimental Stress Models.- 3. Glucagon-Insulin Interactions in Glucoregulation and the Diabetogenic Role of Glucagon.- 4. Glucagon-Insulin-Epinephrine Interactions in Glucoregulation.- 5. Hormonal Regulation of "Futile Cycling"Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Potassium Pump.- IV. Ammonium.- E. Anions.- F. Conclusions.- References.- 27 Cyclic Nucleotides in the Control of Glucagon Secretion.- A. Introduction.- B. Effects of Exogenous Cyclic AMP.- C. Effects of Phosphodiesterase Inhibitors.- D. Effects of Agents Thought to Act via Endogenous Cyclic AMP.- E. Conclusions..- References.- 28 Prostaglandins and Glucagon Secretion.- A. Introduction.- I. Origin and Metabolism of Prostaglandins.- II. Prostaglandins as Local or Intracellular Messengers.- III. Methodological Considerations.- B. Studies In Vitro on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- II. Role of Endogenous Prostaglandins.- 1. Prostaglandin Biosynthesis by Islet Tissue.- 2. Endogenous Prostaglandins and Glucagon Secretion In Vitro.- C. Studies In Vivo on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- 1. Rats.- 2. Dogs.- 3. Humans.- II. Role of Endogenous Prostaglandins.- D. Summary and Conclusions.- References.- 29 Hormones in the Control of Glucagon Secretion.- A. Introduction.- B. Thyroid Hormones.- C. Calcium-Regulating Hormones.- I. Parathyroid Hormone.- II. Calcitonin.- III. Vitamin D.- D. Steroid Hormones.- I. Glucocorticoids.- II. Mineralocorticoids.- III. Sex Steroids.- E. Placental Hormones.- F. Gastrointestinal Hormones.- I. Gastric Inhibitory Polypeptide.- II. Vasoactive Intestinal Peptide.- III. Secretin.- IV. Porcine Intestinal Heptacosapeptide.- V. Bombesin.- VI. Cholecystokinin.- VII. Gastrin.- VIII. Cerulein.- IX. Motilin.- G. Pituitary Hormones.- I. Growth Hormone.- II. Adrenocorticotropic Hormone.- III. Endorphins and Enkephalins.- H. Hypothalamic Hormones.- I. Hypothalamic Lesions.- II. Substance P and Neurotensin.- III. Unidentified Polypeptides.- J. Conclusions.- References.- 30 Neural Control of Glucagon Secretion.- A. Introduction.- B. Anatomic Observations.- I. Neural Pathways.- II. Species Variations.- C. Experimental Observations.- I. Central Nervous System Studies.- II. Nerve Stimulation and Sectioning Studies.- III. Infusion Studies.- D. Physiologic and Pathophysiologic Observations.- E. Neural Control of Gastric Glucagon.- F. Conclusions.- References.- 31 Intraislet Insulin-Glucagon-Somatostatin Relationships.- A. Introduction.- B. Overview of Islet Anatomy.- C. General Mechanisms of Communication Between Cells.- D. Potential Interactions Within Islets.- I. Potential Interactions Between Cells.- 1. Basic Scheme.- 2. Effect of Glucagon Upon B- and D-cells.- 3. Effect of Somatostatin Upon A- und B-cells.- 4. Effect of Insulin Upon A- and D-cells.- 5. Pancreatic Polypeptide as an Ignored Entity and Why.- 6. Other Potential Islet Mediators.- II. Neural Control.- 1. Cholinergic Agonism.- 2. Adrenergic Agonism.- 3. Local Presynaptic Autonomic Regulation.- 4. Peptidergic and Purinergic Regulation.- III. Potential Role of Gap Junctions as Determinants of Coordination Between Islet Cells.- E. Anatomic Determinants of Islet Regulation.- F. Indirect Experimental Evidence for Interaction Between Islet Cells.- G. Efforts to Demonstrate Local Interactions Directly with Immune Neutralization.- H. Arguments Against Islet Interactions.- J. Oscillation of Secretion Suggesting Coordination Between Islets.- K. Consideration of an Islet-Acinar Portal System.- L. Islet Interrelationships in Diabetes.- M. Overview and Conclusions.- References.- 32 Pharmacologic Compounds Affecting Glucagon Secretion.- A. Introduction.- B. Drugs Used in the Treatment of Diabetes.- I. Insulin.- II. Sulfonylureas.- III. Biguanides.- C. Drugs Related to the Cholinergic System.- D. Drugs Related to the Sympathetic Nervous System.- I. Reserpine.- II. Beta-Adrenergic Blocking Agents.- III. Alpha-Adrenergic Blocking Agents.- IV. Clonidine.- V. L-Dopa, Dopamine, and Bromocriptine.- VI. Diazoxide and Tolmesoxide.- E. Serotonin and Serotonin Antagonists.- F. Drugs Affecting Ionic Concentrations and/or Fluxes.- I. Calcium, Calcitonin, and Vitamin D.- II. Verapamil and Procaine.- III. Veratridine, Ouabain, and Hydroquinidine.- G. Drugs Affecting Lipid Metabolism.- H. Drugs Acting on the Central Nervous System.- I. Diphenylhydantoin, Diazepam, and Haloperidol.- II. Morphine, Endorphins, and Enkephalins.- J. Hormonal Steroids.- I. Glucocorticoids.- II. Contraceptive Steroids.- K. Drugs Affecting the Mitotic Spindle.- L. Somatostatin and Somatostatin Analogs.- References.- Extrapancreatic Glucagon.- 33 Extrapancreatic Glucagon and Its Regulation.- A. Introduction.- B. Extrapancreatic Glucagon in the Canine Stomach.- I. Presence of A-cells.- II. Presence of Glucagon.- III. Control of Gastric Glucagon Release In Vitro.- 1. Role of Glucose and Insulin.- 2. Stimulation by Arginine.- 3. Role of the Autonomic Nervous System.- 4. Possible Role of Prostaglandins.- IV. Secretion of Gastric Glucagon In Vivo.- V. Physiologic and Pathophysiologic Relevance of Extrapancreatic Glucagon.- C. Gastrointestinal Glucagon in Other Animal Species.- D. Glucagon and the Salivary Glands.- E. Other Extrapancreatic Localizations of Glucagon.- F. In Vivo Generation of Glucagon from Glucagon-Like Immunoreactive Peptides.- G. Extrapancreatic Glucagon in Humans.- H. Conclusions.- References.- Glucagon in Various Physiological Conditions.- 34 Glucagon and Starvation.- A. Introduction.- B. The Postabsorptive State.- C. Glucoregulatory Hormones in Starvation.- D. Metabolic Alterations in Starvation.- I. The Early Phase.- II. Prolonged Starvation.- E. Summary and Conclusions.- References.- 35 Glucagon and Pregnancy.- A. Introduction.- I. Impaired Glucose Tolerance in Pregnancy.- II. Metabolic Adaptations to Pregnancy.- B. Plasma Glucagon in the Fasted State.- I. Changes After Overnight Fasting.- II. Changes After Prolonged Fasting and Insulin-Induced Hypoglycemia.- III. Placental Transfer of Glucagon and Morphology of A-cells in Pregnancy.- C. Plasma Glucagon in the Fed State.- I. Response to Glucose Administration.- II. Response to Amino Acids.- III. Response to Mixed Meals.- D. Summary and Conclusions.- References.- 36 Glucagon in the Fetus and the Newborn.- A. Introduction.- B. Ontogenesis of Glucagon in Pancreas and Plasma.- I. Rat.- II. Rabbit.- III. Sheep.- IV. Human.- C. Glucagon Secretion in the Fetus.- I. Impermeability of the Placenta to Glucagon.- II. Control of Glucagon Secretion in the Fetus.- 1. Changes in Glucose Concentration.- 2. Effects of Amino Acids.- 3. Effects of Neurotransmitters.- 4. Effects of Hypoxia.- 5. Prolonged Pregnancy.- D. Glucagon Secretion in the Newborn.- I. Evidence for a Role of the Sympathetic Nervous System in the Neonatal Surge of Glucagon.- II. Glucagon Secretion in Newborn Infants of Diabetic Mothers.- III. Glucagon Secretion During the Suckling Period.- IV. Glucagon Secretion During the Weaning Period.- E. Metabolic Effects of Glucagon.- I. In the Fetus.- II. In the Neonate.- III. During the Suckling Period.- IV. During the Weaning Period.- F. Glucagon Receptors in the Perinatal Period.- References.- 37 Glucagon as a Counterregulatory Hormone.- A. Glucose Counterregulation, an Overview.- B. Glucagon in the Prevention of Hypoglycemia.- I. The Postabsorptive State.- II. The Intraprandial State.- C. Glucagon in the Restoration of Normoglycemia.- D. Glucagon and the Somoygi Phenomenon.- E. Summary.- References.- 38 Glucagon and Its Relationship to Other Glucoregulatory Hormones in Exercise and Stress in Normal and Diabetic Subjects.- A. Introduction.- B. Exercise.- I. Metabolic Events During Exercise.- II. Fuel Sources During Exercise.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Changes During Exercise.- IV. Hormonal Interactions in the Control of Glucoregulation During Exercise.- 1. Role of Insulin.- 2. Role of Catecholamines.- 3. Role of Glucagon.- V. The Response to Exercise in Diabetic Subjects.- 1. Exercise in Insulin-Dependent Diabetics.- 2. Exercise in Noninsulin-Dependent Diabetics.- C. Stress.- I. Hormonal Response to Stress.- II. Major Changes in Fuels or Energy Substrate During Stress.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Interactions in Glucoregulation During Stress.- 1. Pathologic Stress States.- 2. Experimental Stress Models.- 3. Glucagon-Insulin Interactions in Glucoregulation and the Diabetogenic Role of Glucagon.- 4. Glucagon-Insulin-Epinephrine Interactions in Glucoregulation.- 5. Hormonal Regulation of "Futile Cycling" in the Liver.- D. Summary.- References.- Catabolism of Glucagon.- 39 The Metabolic Clearance Rate of Glucagon.- A. Introduction.- B. Principles of Measurement.- C. Glucagon Metabolic Clearance Rate in Laboratory Animals.- D. Glucagon Metabolic Clearance Rate in Humans.- E. Organ Contribution to Overall Glucagon Metabolic Clearance Rate.- F. Plasma Half-Life.- G. Summary and Conclusions.- References.- 40 Hepatic Handling of Glucagon.- A. Introduction.- B. Evidence for Glucagon Extraction by the Liver.- I. In Vitro Studies.- II. Relationship Between Portal and Peripheral Vein Glucagon Levels.- III. Studies in Subjects with Portacaval Shunts.- IV. Direct Measurement of Basal Hepatic Extraction of Glucagon.- V. Effect of Glucagon Heterogeneity on Hepatic Glucagon Extraction Rate.- VI. Relationship Between Hepatic Extraction of Glucagon and Insulin.- C. Factors Regulating Hepatic Extraction of Glucagon.- I. Changes in Splanchnic Blood Flow.- II. Anesthesia and Laparotomy.- III. Changes in Portal Vein Glucagon Concentration.- 1. Increased Amount of Glucagon Presented to the Liver.- 2. Decreased Amount of Glucagon Presented to the Liver.- IV. Partial Hepatectomy.- D. Relationship Between Net Hepatic Glucose Output and Glucagon and Insulin.- I. Peripheral Vein Insulin: Glucagon Molar Ratio.- II. Portal Vein Insulin: Glucagon Molar Ratio.- III. Molar Ratio of Insulin and Glucagon Extracted by the Liver.- E. Fate of Glucagon Extracted by the Liver.- F. Conclusions.- References.- 41 The Renal Handling of Glucagon.- A. Introduction.- B. Kidney Glucagon Uptake and Urinary Excretion.- C. Heterogeneity of Plasma Glucagon and Renal Uptake.- D. The Fate of the Glucagon Taken up by the Kidney.- E. Conclusions.- References.- Glucagon in Pathology.- 42 Glucagon Deficiency.- A. Introduction.- B. Chronic Glucagon Deficiency.- I. After Surgical Resection of A-cells.- 1. In Humans.- 2. In Dogs.- 3. In Other Experimental Animals.- II. Idiopathic Chronic Glucagon Deficiency in Neonates.- C. Acute Glucagon Deficiency.- I. After Administration of Anti-Glucagon Sera.- II. After Infusion of Somatostatin.- D. Metabolic Effects of Glucagon Deficiency.- I. On Protein and Amino Acid Metabolism.- II. On Hepatic Glucose Production.- E. Summary and Conclusions.- References.- 43 The Glucagonoma Syndrome.- A. Introduction.- B. Incidence.- I. Age.- II. Sex.- C. Clinical Features.- I. Skin Lesions.- 1. Pathogenesis.- 2. Distribution and Appearance.- 3. Histology.- 4. Differential Diagnosis of Necrolytic Migratory Erythema.- II. Diabetes Mellitus.- III. Anaemia.- IV. Other Features.- D. Biochemical Findings.- I. Plasma Glucagon.- 1. Hyperglucagonaemia: Its Differential Diagnosis.- 2. Glucagon Secretory Patterns.- II. Plasma Insulin.- III. Glucose Tolerance.- IV. Other Peptides Secreted by Glucagonomas.- V. Plasma Amino Acids.- E. Tumour Characteristics.- I. Tumours Associated with the Glucagonoma Syndrome.- 1. Site and Spread.- 2. Light Microscopy.- 3. Immunofluorescence.- 4. Neuron Specific Enolase.- 5. Electron Microscopy.- II. Tumours not Associated with the Glucagonoma Syndrome.- F. Localisation of Tumours.- I. Arteriography.- II. Percutaneous Transhepatic Portal Venous Sampling.- III. Other Techniques.- G. Diagnosis and Treatment.- I. Surgery.- II. Chemotherapy.- III. Antisecretory Therapy.- IV. Hepatic Artery Embolisation.- V. Symptomatic Treatment.- H. Prognosis.- References.- 44 Glucagon in Diabetes Mellitus.- A. A-cell Function in Human Diabetes.- B. Relationships of A-cell Malfunction to Insulin.- C. The Islets in Diabetes: A-cell Relationships Within the Islets.- D. The Effects of Insulin on the A-cell Abnormalities of Type I Diabetics.- E. The Effects of Insulin on A-cell Abnormalities of Type II Diabetics.- F. The Bihormonal Abnormality Hypothesis.- G. The "Glucagon Controversy".- H. Glucagon Suppression as a Therapeutic Adjunct in Diabetes.- References.- 45 Glucagon in Human Endocrine and Exocrine Disorders.- A. Introduction.- B. Human Endocrine Metabolic Disorders.- I. Hypoglycemia.- 1. Hypoglycemia in Infancy and Childhood.- 2. Reactive Hypoglycemia.- 3. Hypoglycemia in Diabetes and in Chronic Pancreatitis.- 4. Glucagon Antibodies.- 5. Beta-Adrenergic Blockade.- II. Hyperglucagonemia.- 1. Glucagonoma.- 2. Nonislet Glucagon-Secreting Tumors.- 3. The Multiple Endocrine Neoplasia.- III. Pheochromocytoma.- IV. Pituitary Interrelationships.- 1. Acromegaly.- 2. Hypopituitarism.- V. Glucagon and the Parathyroid Glands.- 1. Hyperparathyroidism.- 2. Hypoparathyroidism.- VI. Glucagon and Other Endocrine Diseases.- 1. Cushing's Syndrome.- 2. Hyperthyroidism.- 3. Hypothyroidism.- 4. Addison's Disease.- VII. Comment.- C. Glucagon and the Exocrine Pancreas.- I. Interplay with the Islets of Langerhans.- II. Insulin and Glucagon in Pancreatic Exocrine Fluid.- III. Pancreatitis.- References.- 46 Glucagon and Hyperlipoproteinemias.- A. Introduction.- B. The Glucagon-Insulin Environment.- C. Studies in the Zucker Genetic Hyperlipemic Rat.- I. Glucagon Secretion.- II. Glucagon Regulation.- III. Effect of Reduced Glucagon.- IV. Effect of Elevated Insulin.- D. Studies in Human Hyperlipemia.- I. Immunoassayable Glucagon.- II. Hypolipemic Response to Glucagon.- III. Glucagon Structure-Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Potassium Pump.- IV. Ammonium.- E. Anions.- F. Conclusions.- References.- 27 Cyclic Nucleotides in the Control of Glucagon Secretion.- A. Introduction.- B. Effects of Exogenous Cyclic AMP.- C. Effects of Phosphodiesterase Inhibitors.- D. Effects of Agents Thought to Act via Endogenous Cyclic AMP.- E. Conclusions..- References.- 28 Prostaglandins and Glucagon Secretion.- A. Introduction.- I. Origin and Metabolism of Prostaglandins.- II. Prostaglandins as Local or Intracellular Messengers.- III. Methodological Considerations.- B. Studies In Vitro on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- II. Role of Endogenous Prostaglandins.- 1. Prostaglandin Biosynthesis by Islet Tissue.- 2. Endogenous Prostaglandins and Glucagon Secretion In Vitro.- C. Studies In Vivo on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- 1. Rats.- 2. Dogs.- 3. Humans.- II. Role of Endogenous Prostaglandins.- D. Summary and Conclusions.- References.- 29 Hormones in the Control of Glucagon Secretion.- A. Introduction.- B. Thyroid Hormones.- C. Calcium-Regulating Hormones.- I. Parathyroid Hormone.- II. Calcitonin.- III. Vitamin D.- D. Steroid Hormones.- I. Glucocorticoids.- II. Mineralocorticoids.- III. Sex Steroids.- E. Placental Hormones.- F. Gastrointestinal Hormones.- I. Gastric Inhibitory Polypeptide.- II. Vasoactive Intestinal Peptide.- III. Secretin.- IV. Porcine Intestinal Heptacosapeptide.- V. Bombesin.- VI. Cholecystokinin.- VII. Gastrin.- VIII. Cerulein.- IX. Motilin.- G. Pituitary Hormones.- I. Growth Hormone.- II. Adrenocorticotropic Hormone.- III. Endorphins and Enkephalins.- H. Hypothalamic Hormones.- I. Hypothalamic Lesions.- II. Substance P and Neurotensin.- III. Unidentified Polypeptides.- J. Conclusions.- References.- 30 Neural Control of Glucagon Secretion.- A. Introduction.- B. Anatomic Observations.- I. Neural Pathways.- II. Species Variations.- C. Experimental Observations.- I. Central Nervous System Studies.- II. Nerve Stimulation and Sectioning Studies.- III. Infusion Studies.- D. Physiologic and Pathophysiologic Observations.- E. Neural Control of Gastric Glucagon.- F. Conclusions.- References.- 31 Intraislet Insulin-Glucagon-Somatostatin Relationships.- A. Introduction.- B. Overview of Islet Anatomy.- C. General Mechanisms of Communication Between Cells.- D. Potential Interactions Within Islets.- I. Potential Interactions Between Cells.- 1. Basic Scheme.- 2. Effect of Glucagon Upon B- and D-cells.- 3. Effect of Somatostatin Upon A- und B-cells.- 4. Effect of Insulin Upon A- and D-cells.- 5. Pancreatic Polypeptide as an Ignored Entity and Why.- 6. Other Potential Islet Mediators.- II. Neural Control.- 1. Cholinergic Agonism.- 2. Adrenergic Agonism.- 3. Local Presynaptic Autonomic Regulation.- 4. Peptidergic and Purinergic Regulation.- III. Potential Role of Gap Junctions as Determinants of Coordination Between Islet Cells.- E. Anatomic Determinants of Islet Regulation.- F. Indirect Experimental Evidence for Interaction Between Islet Cells.- G. Efforts to Demonstrate Local Interactions Directly with Immune Neutralization.- H. Arguments Against Islet Interactions.- J. Oscillation of Secretion Suggesting Coordination Between Islets.- K. Consideration of an Islet-Acinar Portal System.- L. Islet Interrelationships in Diabetes.- M. Overview and Conclusions.- References.- 32 Pharmacologic Compounds Affecting Glucagon Secretion.- A. Introduction.- B. Drugs Used in the Treatment of Diabetes.- I. Insulin.- II. Sulfonylureas.- III. Biguanides.- C. Drugs Related to the Cholinergic System.- D. Drugs Related to the Sympathetic Nervous System.- I. Reserpine.- II. Beta-Adrenergic Blocking Agents.- III. Alpha-Adrenergic Blocking Agents.- IV. Clonidine.- V. L-Dopa, Dopamine, and Bromocriptine.- VI. Diazoxide and Tolmesoxide.- E. Serotonin and Serotonin Antagonists.- F. Drugs Affecting Ionic Concentrations and/or Fluxes.- I. Calcium, Calcitonin, and Vitamin D.- II. Verapamil and Procaine.- III. Veratridine, Ouabain, and Hydroquinidine.- G. Drugs Affecting Lipid Metabolism.- H. Drugs Acting on the Central Nervous System.- I. Diphenylhydantoin, Diazepam, and Haloperidol.- II. Morphine, Endorphins, and Enkephalins.- J. Hormonal Steroids.- I. Glucocorticoids.- II. Contraceptive Steroids.- K. Drugs Affecting the Mitotic Spindle.- L. Somatostatin and Somatostatin Analogs.- References.- Extrapancreatic Glucagon.- 33 Extrapancreatic Glucagon and Its Regulation.- A. Introduction.- B. Extrapancreatic Glucagon in the Canine Stomach.- I. Presence of A-cells.- II. Presence of Glucagon.- III. Control of Gastric Glucagon Release In Vitro.- 1. Role of Glucose and Insulin.- 2. Stimulation by Arginine.- 3. Role of the Autonomic Nervous System.- 4. Possible Role of Prostaglandins.- IV. Secretion of Gastric Glucagon In Vivo.- V. Physiologic and Pathophysiologic Relevance of Extrapancreatic Glucagon.- C. Gastrointestinal Glucagon in Other Animal Species.- D. Glucagon and the Salivary Glands.- E. Other Extrapancreatic Localizations of Glucagon.- F. In Vivo Generation of Glucagon from Glucagon-Like Immunoreactive Peptides.- G. Extrapancreatic Glucagon in Humans.- H. Conclusions.- References.- Glucagon in Various Physiological Conditions.- 34 Glucagon and Starvation.- A. Introduction.- B. The Postabsorptive State.- C. Glucoregulatory Hormones in Starvation.- D. Metabolic Alterations in Starvation.- I. The Early Phase.- II. Prolonged Starvation.- E. Summary and Conclusions.- References.- 35 Glucagon and Pregnancy.- A. Introduction.- I. Impaired Glucose Tolerance in Pregnancy.- II. Metabolic Adaptations to Pregnancy.- B. Plasma Glucagon in the Fasted State.- I. Changes After Overnight Fasting.- II. Changes After Prolonged Fasting and Insulin-Induced Hypoglycemia.- III. Placental Transfer of Glucagon and Morphology of A-cells in Pregnancy.- C. Plasma Glucagon in the Fed State.- I. Response to Glucose Administration.- II. Response to Amino Acids.- III. Response to Mixed Meals.- D. Summary and Conclusions.- References.- 36 Glucagon in the Fetus and the Newborn.- A. Introduction.- B. Ontogenesis of Glucagon in Pancreas and Plasma.- I. Rat.- II. Rabbit.- III. Sheep.- IV. Human.- C. Glucagon Secretion in the Fetus.- I. Impermeability of the Placenta to Glucagon.- II. Control of Glucagon Secretion in the Fetus.- 1. Changes in Glucose Concentration.- 2. Effects of Amino Acids.- 3. Effects of Neurotransmitters.- 4. Effects of Hypoxia.- 5. Prolonged Pregnancy.- D. Glucagon Secretion in the Newborn.- I. Evidence for a Role of the Sympathetic Nervous System in the Neonatal Surge of Glucagon.- II. Glucagon Secretion in Newborn Infants of Diabetic Mothers.- III. Glucagon Secretion During the Suckling Period.- IV. Glucagon Secretion During the Weaning Period.- E. Metabolic Effects of Glucagon.- I. In the Fetus.- II. In the Neonate.- III. During the Suckling Period.- IV. During the Weaning Period.- F. Glucagon Receptors in the Perinatal Period.- References.- 37 Glucagon as a Counterregulatory Hormone.- A. Glucose Counterregulation, an Overview.- B. Glucagon in the Prevention of Hypoglycemia.- I. The Postabsorptive State.- II. The Intraprandial State.- C. Glucagon in the Restoration of Normoglycemia.- D. Glucagon and the Somoygi Phenomenon.- E. Summary.- References.- 38 Glucagon and Its Relationship to Other Glucoregulatory Hormones in Exercise and Stress in Normal and Diabetic Subjects.- A. Introduction.- B. Exercise.- I. Metabolic Events During Exercise.- II. Fuel Sources During Exercise.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Changes During Exercise.- IV. Hormonal Interactions in the Control of Glucoregulation During Exercise.- 1. Role of Insulin.- 2. Role of Catecholamines.- 3. Role of Glucagon.- V. The Response to Exercise in Diabetic Subjects.- 1. Exercise in Insulin-Dependent Diabetics.- 2. Exercise in Noninsulin-Dependent Diabetics.- C. Stress.- I. Hormonal Response to Stress.- II. Major Changes in Fuels or Energy Substrate During Stress.- 1. Carbohydrate-Derived Fuels.- 2. Fat-Derived Fuels.- 3. Protein-Derived Fuels.- III. Hormonal Interactions in Glucoregulation During Stress.- 1. Pathologic Stress States.- 2. Experimental Stress Models.- 3. Glucagon-Insulin Interactions in Glucoregulation and the Diabetogenic Role of Glucagon.- 4. Glucagon-Insulin-Epinephrine Interactions in Glucoregulation.- 5. Hormonal Regulation of "Futile Cycling" in the Liver.- D. Summary.- References.- Catabolism of Glucagon.- 39 The Metabolic Clearance Rate of Glucagon.- A. Introduction.- B. Principles of Measurement.- C. Glucagon Metabolic Clearance Rate in Laboratory Animals.- D. Glucagon Metabolic Clearance Rate in Humans.- E. Organ Contribution to Overall Glucagon Metabolic Clearance Rate.- F. Plasma Half-Life.- G. Summary and Conclusions.- References.- 40 Hepatic Handling of Glucagon.- A. Introduction.- B. Evidence for Glucagon Extraction by the Liver.- I. In Vitro Studies.- II. Relationship Between Portal and Peripheral Vein Glucagon Levels.- III. Studies in Subjects with Portacaval Shunts.- IV. Direct Measurement of Basal Hepatic Extraction of Glucagon.- V. Effect of Glucagon Heterogeneity on Hepatic Glucagon Extraction Rate.- VI. Relationship Between Hepatic Extraction of Glucagon and Insulin.- C. Factors Regulating Hepatic Extraction of Glucagon.- I. Changes in Splanchnic Blood Flow.- II. Anesthesia and Laparotomy.- III. Changes in Portal Vein Glucagon Concentration.- 1. Increased Amount of Glucagon Presented to the Liver.- 2. Decreased Amount of Glucagon Presented to the Liver.- IV. Partial Hepatectomy.- D. Relationship Between Net Hepatic Glucose Output and Glucagon and Insulin.- I. Peripheral Vein Insulin: Glucagon Molar Ratio.- II. Portal Vein Insulin: Glucagon Molar Ratio.- III. Molar Ratio of Insulin and Glucagon Extracted by the Liver.- E. Fate of Glucagon Extracted by the Liver.- F. Conclusions.- References.- 41 The Renal Handling of Glucagon.- A. Introduction.- B. Kidney Glucagon Uptake and Urinary Excretion.- C. Heterogeneity of Plasma Glucagon and Renal Uptake.- D. The Fate of the Glucagon Taken up by the Kidney.- E. Conclusions.- References.- Glucagon in Pathology.- 42 Glucagon Deficiency.- A. Introduction.- B. Chronic Glucagon Deficiency.- I. After Surgical Resection of A-cells.- 1. In Humans.- 2. In Dogs.- 3. In Other Experimental Animals.- II. Idiopathic Chronic Glucagon Deficiency in Neonates.- C. Acute Glucagon Deficiency.- I. After Administration of Anti-Glucagon Sera.- II. After Infusion of Somatostatin.- D. Metabolic Effects of Glucagon Deficiency.- I. On Protein and Amino Acid Metabolism.- II. On Hepatic Glucose Production.- E. Summary and Conclusions.- References.- 43 The Glucagonoma Syndrome.- A. Introduction.- B. Incidence.- I. Age.- II. Sex.- C. Clinical Features.- I. Skin Lesions.- 1. Pathogenesis.- 2. Distribution and Appearance.- 3. Histology.- 4. Differential Diagnosis of Necrolytic Migratory Erythema.- II. Diabetes Mellitus.- III. Anaemia.- IV. Other Features.- D. Biochemical Findings.- I. Plasma Glucagon.- 1. Hyperglucagonaemia: Its Differential Diagnosis.- 2. Glucagon Secretory Patterns.- II. Plasma Insulin.- III. Glucose Tolerance.- IV. Other Peptides Secreted by Glucagonomas.- V. Plasma Amino Acids.- E. Tumour Characteristics.- I. Tumours Associated with the Glucagonoma Syndrome.- 1. Site and Spread.- 2. Light Microscopy.- 3. Immunofluorescence.- 4. Neuron Specific Enolase.- 5. Electron Microscopy.- II. Tumours not Associated with the Glucagonoma Syndrome.- F. Localisation of Tumours.- I. Arteriography.- II. Percutaneous Transhepatic Portal Venous Sampling.- III. Other Techniques.- G. Diagnosis and Treatment.- I. Surgery.- II. Chemotherapy.- III. Antisecretory Therapy.- IV. Hepatic Artery Embolisation.- V. Symptomatic Treatment.- H. Prognosis.- References.- 44 Glucagon in Diabetes Mellitus.- A. A-cell Function in Human Diabetes.- B. Relationships of A-cell Malfunction to Insulin.- C. The Islets in Diabetes: A-cell Relationships Within the Islets.- D. The Effects of Insulin on the A-cell Abnormalities of Type I Diabetics.- E. The Effects of Insulin on A-cell Abnormalities of Type II Diabetics.- F. The Bihormonal Abnormality Hypothesis.- G. The "Glucagon Controversy".- H. Glucagon Suppression as a Therapeutic Adjunct in Diabetes.- References.- 45 Glucagon in Human Endocrine and Exocrine Disorders.- A. Introduction.- B. Human Endocrine Metabolic Disorders.- I. Hypoglycemia.- 1. Hypoglycemia in Infancy and Childhood.- 2. Reactive Hypoglycemia.- 3. Hypoglycemia in Diabetes and in Chronic Pancreatitis.- 4. Glucagon Antibodies.- 5. Beta-Adrenergic Blockade.- II. Hyperglucagonemia.- 1. Glucagonoma.- 2. Nonislet Glucagon-Secreting Tumors.- 3. The Multiple Endocrine Neoplasia.- III. Pheochromocytoma.- IV. Pituitary Interrelationships.- 1. Acromegaly.- 2. Hypopituitarism.- V. Glucagon and the Parathyroid Glands.- 1. Hyperparathyroidism.- 2. Hypoparathyroidism.- VI. Glucagon and Other Endocrine Diseases.- 1. Cushing's Syndrome.- 2. Hyperthyroidism.- 3. Hypothyroidism.- 4. Addison's Disease.- VII. Comment.- C. Glucagon and the Exocrine Pancreas.- I. Interplay with the Islets of Langerhans.- II. Insulin and Glucagon in Pancreatic Exocrine Fluid.- III. Pancreatitis.- References.- 46 Glucagon and Hyperlipoproteinemias.- A. Introduction.- B. The Glucagon-Insulin Environment.- C. Studies in the Zucker Genetic Hyperlipemic Rat.- I. Glucagon Secretion.- II. Glucagon Regulation.- III. Effect of Reduced Glucagon.- IV. Effect of Elevated Insulin.- D. Studies in Human Hyperlipemia.- I. Immunoassayable Glucagon.- II. Hypolipemic Response to Glucagon.- III. Glucagon Structure-Function Relationships.- IV. Response to Therapy.- E. The Mechanism of the Hypolipemic Response to Glucagon.- References.- 47 Glucagon and Renal Insufficiency.- A. Introduction.- B. The Effects of Renal Failure on Circulating Glucagon Levels and Molecular Profiles.- C. The Effects of Renal Failure on Glucagon Secretion, Biologic Action, and Receptor Binding.- I. Glucagon Secretion.- II. Biologic Activity.- III. Receptor Binding.- D. The Role of Abnormalities in Glucagon Levels and Action in the Metabolic Disturbances of Uremia.- I. Glucose Intolerance.- 1. Hyperglucagonemia and Hepatic Glucose Production.- 2. Increased Tissue Sensitivity to Glucagon.- II. Hypoglycemia.- E. Summary and Conclusions.- References.- 48 Glucagon in Cirrhosis of the Liver.- A. Introduction.- B. Plasma Glucagon Levels in Cirrhotic Patients.- I. In the Basal State.- II. After A-cell Stimulation.- III. After A-cell Inhibition.- C. The Cause of Hyperglucagonism in Cirrhotic Patients.- I. The Role of Portasystemic Shunting.- II. The Role of Hepatocellular Damage.- III. Other Factors.- D. Plasma Glucagon-Like Immunoreactivity Levels in Cirrhotic Patients.- E. The Nature of Circulating Immunoreactive Glucagon in Cirrhotic Patients.- F. Pathogenic Implications of Hyperglucagonemia in Cirrhosis of the Liver.- G. Summary.- References.- 49 Glucagon in Obesity.- A. Introduction.- B. Glucagon in Human Obesity.- I. Plasma Concentrations of Glucagon.- 1. Basal State.- 2. Tests of A-cell Function.- II. Effect of Glucagon in Human Obesity.- C. Experimental Obesity.- I. The Obese Mouse.- II. The Zucker Rat.- III. Rats with Dietary Obesity.- IV. VMH Rats.- D. Extrapancreatic Glucagon in Obesity.- References.- Pharmacological Effects of Glucagon and the Use of Glucagon for Diagnosis and in Therapeutics.- 50 Influence of Glucagon on Water and Electrolyte Metabolism.- A. Introduction.- B. The Kidney as a Target Site for Glucagon Action on Water and Mineral Metabolism.- I. Renal Extraction, Handling, and Metabolism of Glucagon.- II. Direct Effect of Glucagon on Renal Function.- 1. Glucagon-Induced Increase in the Glomerular Filtration Rate.- 2. Influence of Glucagon on Renal Hemodynamics.- 3. Postulated Direct Effect of Glucagon on Tubular Function.- C. The Influence of Glucagon on Natriuresis of Starvation.- D. The Effect of Glucagon on Plasma Electrolyte Levels.- I. Hypocalcemic Effect of Glucagon.- II. Glucagon-Induced Decrease in Plasma Phosphate Levels.- III. Influence of Glucagon on Plasma Potassium Levels.- E. Summary and Conclusions.- References.- 51 Glucagon and Catecholamines.- A. Introduction.- B. Glucagon and Catecholamine Release In Vitro.- C. Glucagon and Catecholamine Release In Vivo.- I. Rats.- II. Guinea Pigs.- III. Dogs.- IV. Cats.- V. Humans.- 1. Plasma Catecholamines.- 2. Urinary Catecholamines and Metabolites.- D. Glucagon and Pheochromocytoma.- I. Glucagon as a Provocative Test in Pheochromocytoma.- II. Mode of Action of Glucagon in Pheochromocytoma.- E. Conclusions.- References.- 52 Glucagon and Growth Hormone.- A. Introduction.- B. Acute and Chronic Effects of Growth Hormone on Glucagon Secretion.- C. Effect of Glucagon on Growth Hormone Secretion.- D. Summary.- References.- 53 Glucagon and the Heart.- A. Introduction.- B. Effects of Glucagon on Mechanical and Electrophysiologic Properties.- I. Cardiac Contractility and Rate.- II. Atrioventricular Conduction and Idioventricular Rhythms.- III. Cardiac Action Potentials.- IV. Coronary Blood Flow and Cardiac Oxygen Consumption.- C. Factors Which Influence Inotropic and Chronotropic Effects.- I. Species Differences.- II. Temperature Effects.- III. Rate-Force Relationship.- IV. Heart Failure.- V. Hypertension.- VI. Age.- VII. Ionic Composition.- VIII. Adrenergic Blocking Agents.- IX. The Interaction of Glucagon with Phosphodiesterase Inhibitors.- X. Interaction of Glucagon with Cardiac Glycosides.- D. Glucagon and Cyclic AMP Formation in Cardiac Muscle.- E. Glucagon, Cyclic AMP, and Calcium Ion Fluxes.- F. Effects of Glucagon on Cardiac Carbohydrate Metabolism.- G. Effects of Glucagon on Cardiac Lipid Metabolism.- H. Relation of the Metabolic Effects of Glucagon to Cardiac Potassium Metabolism.- J. Glucagon-Receptor Interactions.- K. Desensitization.- L. Clinical Studies with Glucagon.- M. Conclusions.- References.- 54 Spasmolytic Action and Clinical Use of Glucagon.- A. Spasmolytic Effects of Glucagon in Various Species.- I. Mechanisms of Action.- II. Structure-Activity Relationships.- III. Conclusions.- B. Clinical Use of Glucagon as a Spasmolytic or Hypotonic Drug...#8212
- Function Relationships.- IV. Response to Therapy.- E. The Mechanism of the Hypolipemic Response to Glucagon.- References.- 47 Glucagon and Renal Insufficiency.- A. Introduction.- B. The Effects of Renal Failure on Circulating Glucagon Levels and Molecular Profiles.- C. The Effects of Renal Failure on Glucagon Secretion, Biologic Action, and Receptor Binding.- I. Glucagon Secretion.- II. Biologic Activity.- III. Receptor Binding.- D. The Role of Abnormalities in Glucagon Levels and Action in the Metabolic Disturbances of Uremia.- I. Glucose Intolerance.- 1. Hyperglucagonemia and Hepatic Glucose Production.- 2. Increased Tissue Sensitivity to Glucagon.- II. Hypoglycemia.- E. Summary and Conclusions.- References.- 48 Glucagon in Cirrhosis of the Liver.- A. Introduction.- B. Plasma Glucagon Levels in Cirrhotic Patients.- I. In the Basal State.- II. After A-cell Stimulation.- III. After A-cell Inhibition.- C. The Cause of Hyperglucagonism in Cirrhotic Patients.- I. The Role of Portasystemic Shunting.- II. The Role of Hepatocellular Damage.- III. Other Factors.- D. Plasma Glucagon-Like Immunoreactivity Levels in Cirrhotic Patients.- E. The Nature of Circulating Immunoreactive Glucagon in Cirrhotic Patients.- F. Pathogenic Implications of Hyperglucagonemia in Cirrhosis of the Liver.- G. Summary.- References.- 49 Glucagon in Obesity.- A. Introduction.- B. Glucagon in Human Obesity.- I. Plasma Concentrations of Glucagon.- 1. Basal State.- 2. Tests of A-cell Function.- II. Effect of Glucagon in Human Obesity.- C. Experimental Obesity.- I. The Obese Mouse.- II. The Zucker Rat.- III. Rats with Dietary Obesity.- IV. VMH Rats.- D. Extrapancreatic Glucagon in Obesity.- References.- Pharmacological Effects of Glucagon and the Use of Glucagon for Diagnosis and in Therapeutics.- 50 Influence of Glucagon on Water and Electrolyte Metabolism.- A. Introduction.- B. The Kidney as a Target Site for Glucagon Action on Water and Mineral Metabolism.- I. Renal Extraction, Handling, and Metabolism of Glucagon.- II. Direct Effect of Glucagon on Renal Function.- 1. Glucagon-Induced Increase in the Glomerular Filtration Rate.- 2. Influence of Glucagon on Renal Hemodynamics.- 3. Postulated Direct Effect of Glucagon on Tubular Function.- C. The Influence of Glucagon on Natriuresis of Starvation.- D. The Effect of Glucagon on Plasma Electrolyte Levels.- I. Hypocalcemic Effect of Glucagon.- II. Glucagon-Induced Decrease in Plasma Phosphate Levels.- III. Influence of Glucagon on Plasma Potassium Levels.- E. Summary and Conclusions.- References.- 51 Glucagon and Catecholamines.- A. Introduction.- B. Glucagon and Catecholamine Release In Vitro.- C. Glucagon and Catecholamine Release In Vivo.- I. Rats.- II. Guinea Pigs.- III. Dogs.- IV. Cats.- V. Humans.- 1. Plasma Catecholamines.- 2. Urinary Catecholamines and Metabolites.- D. Glucagon and Pheochromocytoma.- I. Glucagon as a Provocative Test in Pheochromocytoma.- II. Mode of Action of Glucagon in Pheochromocytoma.- E. Conclusions.- References.- 52 Glucagon and Growth Hormone.- A. Introduction.- B. Acute and Chronic Effects of Growth Hormone on Glucagon Secretion.- C. Effect of Glucagon on Growth Hormone Secretion.- D. Summary.- References.- 53 Glucagon and the Heart.- A. Introduction.- B. Effects of Glucagon on Mechanical and Electrophysiologic Properties.- I. Cardiac Contractility and Rate.- II. Atrioventricular Conduction and Idioventricular Rhythms.- III. Cardiac Action Potentials.- IV. Coronary Blood Flow and Cardiac Oxygen Consumption.- C. Factors Which Influence Inotropic and Chronotropic Effects.- I. Species Differences.- II. Temperature Effects.- III. Rate-Force Relationship.- IV. Heart Failure.- V. Hypertension.- VI. Age.- VII. Ionic Composition.- VIII. Adrenergic Blocking Agents.- IX. The Interaction of Glucagon with Phosphodiesterase Inhibitors.- X. Interaction of Glucagon with Cardiac Glycosides.- D. Glucagon and Cyclic AMP Formation in Cardiac Muscle.- E. Glucagon, Cyclic AMP, and Calcium Ion Fluxes.- F. Effects of Glucagon on Cardiac Carbohydrate Metabolism.- G. Effects of Glucagon on Cardiac Lipid Metabolism.- H. Relation of the Metabolic Effects of Glucagon to Cardiac Potassium Metabolism.- J. Glucagon-Receptor Interactions.- K. Desensitization.- L. Clinical Studies with Glucagon.- M. Conclusions.- References.- 54 Spasmolytic Action and Clinical Use of Glucagon.- A. Spasmolytic Effects of Glucagon in Various Species.- I. Mechanisms of Action.- II. Structure-Activity Relationships.- III. Conclusions.- B. Clinical Use of Glucagon as a Spasmolytic or Hypotonic Drug...Microfilamentous System.- II. How Do Amino Acids Trigger Glucagon Release?.- III. Contribution of the Adenylate Cyclase System and of Ca2+ and Other Ion Fluxes.- IV. Relative Resistance of A-cell Function to Hypothermia.- D. Modulation of Amino Acid-Induced Glucagon Release.- I. Major Role of Glucose and Insulin Concentrations.- 1. Role of Glucose in Nondiabetic Subjects.- 2. Role of Insulin.- 3. Studies in Diabetic Subjects.- II. Other Physiologic Modulations.- 1. Short-Term Modulations.- 2. Long-Term Modulations.- III. Other Pathophysiologic Modulations.- 1. Liver Cirrhosis.- 2. Kidney Failure.- 3. Thyroid Conditions.- 4. The Somatostatinoma Syndrome.- 5. The Glucagonoma Syndrome.- 6. Obese Nondiabetic Patients.- 7. Pheochromocytoma.- 8. Stress.- E. Amino Acid-Induced Glucagon Release and the Regulation of Substrate Distribution.- I. Physiologic Relevance of the Amino Acid and Glucagon Concentrations.- 1. Blood Amino Acid Concentration.- 2. Plasma Glucagon Concentration and Biologic Efficacy.- II. Clinical Correlations.- 1. Normal Subjects.- 2. Insulin-Dependent Patients.- References.- 25 Free Fatty Acids and Glucagon Secretion.- A. Introduction.- B. In Vitro Studies.- I. Isolated Islets.- II. Isolated Perfused Rat Pancreas.- C. Experiments in Animals.- I. Dogs.- II. Rats.- III. Ducks.- D. Studies in Humans.- I. Normal Subjects.- II. Pregnant Women.- III. Diabetes.- IV. Hypertriglyceridemia.- E. The Modulating Role of Circulating FFA on Glucagon Secretion.- I. Mechanism of Action of FFA on A-cells.- II. Possible Significance of the Role of FFA in the Regulation of A-cell Secretion.- References.- 26 Ions in the Control of Glucagon Release.- A. Introduction.- B. Calcium and Glucagon Release.- I. The Inhibitory Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- II. The Positive Modulating Role of Calcium.- 1. Experimental Data.- 2. Possible Mechanisms of Action.- III. The Recognition Role of Calcium.- IV. The In Vivo Effects of Calcium.- V. Conclusions.- C. Other Divalent Cations.- I. Magnesium.- II. Manganese.- III. Miscellaneous Cations.- D. Monovalent Cations.- I. Potassium.- II. Sodium.- III. The Sodium-Potassium Pump.- IV. Ammonium.- E. Anions.- F. Conclusions.- References.- 27 Cyclic Nucleotides in the Control of Glucagon Secretion.- A. Introduction.- B. Effects of Exogenous Cyclic AMP.- C. Effects of Phosphodiesterase Inhibitors.- D. Effects of Agents Thought to Act via Endogenous Cyclic AMP.- E. Conclusions..- References.- 28 Prostaglandins and Glucagon Secretion.- A. Introduction.- I. Origin and Metabolism of Prostaglandins.- II. Prostaglandins as Local or Intracellular Messengers.- III. Methodological Considerations.- B. Studies In Vitro on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- II. Role of Endogenous Prostaglandins.- 1. Prostaglandin Biosynthesis by Islet Tissue.- 2. Endogenous Prostaglandins and Glucagon Secretion In Vitro.- C. Studies In Vivo on the Influence of Prostaglandins on Glucagon Secretion.- I. Effect of Exogenous Prostaglandins.- 1. Rats.- 2. Dogs.- 3. Humans.- II. Role of Endogenous Prostaglandins.- D. Summary and Conclusions.- References.- 29 Hormones in the Control of Glucagon Secretion.- A. Introduction.- B. Thyroid Hormones.- C. Calcium-Regulating Hormones.- I. Parathyroid Hormone.- II. Calcitonin.- III. Vitamin D.- D. Steroid Hormones.- I. Glucocorticoids.- II. Mineralocorticoids.- III. Sex Steroids.- E. Placental Hormones.- F. Gastrointestinal Hormones.- I. Gastric Inhibitory Polypeptide.- II. Vasoactive Intestinal Peptide.- III. Secretin.- IV. Porcine Intestinal Heptacosapeptide.- V. Bombesin.- VI. Cholecystokinin.- VII. Gastrin.- VIII. Cerulein.- IX. Motilin.- G. Pituitary Hormones.- I. Growth Hormone.- II. Adrenocorticotropic Hormone.- III. Endorphins and Enkephalins.- H. Hypothalamic Hormones.- I. Hypothalamic Lesions.- II. Substance P and Neurotensin.- III. Unidentified Polypeptides.- J. Conclusions.- References.- 30 Neural Control of Glucagon Secretion.- A. Introduction.- B. Anatomic Observations.- I. Neural Pathways.- II. Species Variations.- C. Experimental Observations.- I. Central Nervous System Studies.- II. Nerve Stimulation and Sectioning Studies.- III. Infusion Studies.- D. Physiologic and Pathophysiologic Observations.- E. Neural Control of Gastric Glucagon.- F. Conclusions.- References.- 31 Intraislet Insulin-Glucagon-Somatostatin Relationships.- A. Introduction.- B. Overview of Islet Anatomy.- C. General Mechanisms of Communication Between Cells.- D. Potential Interactions Within Islets.- I. Potential Interactions Between Cells.- 1. Basic Scheme.- 2. Effect of Glucagon Upon B- and D-cells.- 3. Effect of Somatostatin Upon A- und B-cells.- 4. Effect of Insulin Upon A- and D-cells.- 5. Pancreatic Polypeptide as an Ignored Entity and Why.- 6. Other Potential Islet Mediators.- II. Neural Control.- 1. Cholinergic Agonism.- 2. Adrenergic Agonism.- 3. Local Presynaptic Autonomic Regulation.- 4. Peptidergic and Purinergic Regulation.- III. Potential Role of Gap Junctions as Determinants of Coordination Between Islet Cells.- E. Anatomic Determinants of Islet Regulation.- F. Indirect Experimental Evidence for Interaction Between Islet Cells.- G. Efforts to Demonstrate Local Interactions Directly with Immune Neutralization.- H. Arguments Against Islet Interactions.- J. Oscillation of Secretion Suggesting Coordination Between Islets.- K. Consideration of an Islet-Acinar Portal System.- L. Islet Interrelationships in Diabetes.- M. Overview and Conclusions.- References.- 32 Pharmacologic Compounds Affecting Glucagon Secretion.- A. Introduction.- B. Drugs Used in the Treatment of Diabetes.- I. Insulin.- II. Sulfonylureas.- III. Biguanides.- C. Drugs Related to the Cholinergic System.- D. Drugs Related to the Sympathetic Nervous System.- I. Reserpine.- II. Beta-Adrenergic Blocking Agents.- III. Alpha-Adrenergic Blocking Agents.- IV. Clonidine.- V. L-Dopa, Dopamine, and Bromocriptine.- VI. Diazoxide and Tolmesoxide.- E. Serotonin and Sero
- Volume
-
3 ISBN 9783540609896
Description
by "Nielsen BookData"