Involvement of AMP-Activated Protein Kinase in Glucose Uptake Stimulated by the Globular Domain of Adiponectin in Primary Rat Adipocytes

• Xiangdong Wu

  Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

• Hiroyuki Motoshima

  Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

• Kalyankar Mahadev

  Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

• Timothy J. Stalker

  Department of Physiology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

• Rosario Scalia

  Department of Physiology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

• Barry J. Goldstein

  Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

抄録

Adiponectin is an abundant adipocyte-derived plasma protein with anti-atherosclerotic and insulin-sensitizing properties that suppresses hepatic glucose production and enhances glucose uptake into skeletal muscle. To characterize the potential effects of adiponectin on glucose uptake into adipose cells, we incubated isolated epididymal rat adipocytes with the globular domain of recombinant adiponectin purified from an E. coli expression system. Globular adiponectin increased glucose uptake in adipocytes without stimulating tyrosine phosphorylation of the insulin receptor or insulin receptor substrate-1, and without enhancing phosphorylation of Akt on Ser-473. Globular adiponectin further enhanced insulin-stimulated glucose uptake at submaximal insulin concentrations and reversed the inhibitory effect of tumor necrosis factor-α on insulin-stimulated glucose uptake. Cellular treatment with globular adiponectin increased the Thr-172 phosphorylation and catalytic activity of AMP-activated protein kinase and enhanced the Ser-79 phosphorylation of acetyl CoA carboxylase, an enzyme downstream of AMP kinase in adipose cells. Inhibition of AMP kinase activation using two pharmacological inhibitors (adenine 9-β-d-arabinofuranoside and compound C) completely abrogated the increase in glucose uptake stimulated by globular adiponectin, indicating that AMP kinase is integrally involved in the adiponectin signal transduction pathway. Coupled with recent evidence that the effects of adiponectin are mediated via AMP kinase activation in liver and skeletal muscle, the findings reported here provide an important mechanistic link in the signaling effects of adiponectin in diverse metabolically responsive tissues.

収録刊行物

• Diabetes

  Diabetes 52 (6), 1355-1363, 2003-06-01

  American Diabetes Association

キーワード

• Endocrinology, Diabetes and Metabolism
• Internal Medicine

詳細情報

• CRID: 1364233270532297216
• NII論文ID: 30026273045
• DOI: 10.2337/diabetes.52.6.1355
• ISSN: 1939327X
• ISSN: 00121797
• ISSN: http://id.crossref.org/issn/00121797
• Web Site: https://journals.org/diabetes/diabetes/article-pdf/52/6/1355/374939/db0603001355.pdf
• Web Site: https://diabetesjournals.org/diabetes/article-pdf/52/6/1355/374939/db0603001355.pdf
• データソース種別:
  • Crossref
  • CiNii Articles