Effects of Tungstate, a New Potential Oral Antidiabetic Agent, in Zucker Diabetic Fatty Rats

• María Carmen Muñoz

  From the Department of Biochemistry and Molecular Biology (M.C.M., A.B., J.D., J.J.G.), Universitat de Barcelona; and the Endocrinology and Diabetes Unit (J.F.-A., R.G.), Department of Medicine, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic i Universitari, Barcelona, Spain.

• Albert Barberà

  From the Department of Biochemistry and Molecular Biology (M.C.M., A.B., J.D., J.J.G.), Universitat de Barcelona; and the Endocrinology and Diabetes Unit (J.F.-A., R.G.), Department of Medicine, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic i Universitari, Barcelona, Spain.

• Jorge Domínguez

  From the Department of Biochemistry and Molecular Biology (M.C.M., A.B., J.D., J.J.G.), Universitat de Barcelona; and the Endocrinology and Diabetes Unit (J.F.-A., R.G.), Department of Medicine, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic i Universitari, Barcelona, Spain.

• Josefa Fernàndez-Alvarez

  From the Department of Biochemistry and Molecular Biology (M.C.M., A.B., J.D., J.J.G.), Universitat de Barcelona; and the Endocrinology and Diabetes Unit (J.F.-A., R.G.), Department of Medicine, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic i Universitari, Barcelona, Spain.

• Ramon Gomis

  From the Department of Biochemistry and Molecular Biology (M.C.M., A.B., J.D., J.J.G.), Universitat de Barcelona; and the Endocrinology and Diabetes Unit (J.F.-A., R.G.), Department of Medicine, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic i Universitari, Barcelona, Spain.

• Joan J. Guinovart

  From the Department of Biochemistry and Molecular Biology (M.C.M., A.B., J.D., J.J.G.), Universitat de Barcelona; and the Endocrinology and Diabetes Unit (J.F.-A., R.G.), Department of Medicine, Institut d'Investigacions Biomèdiques Agustí Pi i Sunyer, Hospital Clínic i Universitari, Barcelona, Spain.

抄録

Tungstate was orally administered to 7.5-week-old male Zucker diabetic fatty (ZDF) rats that already showed moderate hyperglycemia (180 ± 16 mg/dl). The animals became normoglycemic for ∼10 days. Then, glycemia started to rise again, although it did not reach the initial values until day 24, when levels stabilized at ∼200 mg/dl for the duration of the experiment. Untreated ZDF rats showed steadily increased blood glucose levels between 7.5 and 10 weeks of age, when they reached a maximum value of 450 ± 19 mg/dl, which was maintained throughout the experiment. In addition, tolerance to intraperitoneal glucose load improved in treated diabetic rats. Serum levels of triglycerides were elevated in untreated diabetic rats compared with their lean counterparts (ZLC). In the liver of diabetic animals, glucokinase (GK), glycogen phosphorylase a (GPa), liverpyruvate kinase (L-PK), and fatty acid synthase (FAS) activities decreased by 81, 30, 54, and 35%, respectively, whereas phosphoenolpyruvate carboxykinase (PEPCK) levels increased by 240%. Intracellular glucose-6-phosphate (G6P) decreased by 40%, whereas glycogen levels remained unaffected. Tungstate treatment of these rats induced a 42% decrease in serum levels of triglycerides and normalized hepatic G6P concentrations, GPa activity, and PEPCK levels. GK activity in treated diabetic rats increased to 50% of the values of untreated ZLC rats. L-PK and FAS activity increased to higher values than those in untreated lean rats (1.7-fold L-PK and 2.4-fold FAS). Hepatic glycogen levels were 55% higher than those in untreated diabetic and healthy rats. Tungstate treatment did not significantly change the phosphotyrosine protein profile of primary cultured hepatocytes from diabetic animals. These data suggest that tungstate administration to ZDF rats causes a considerable reduction of glycemia, mainly through a partial restoration of hepatic glucose metabolism and a decrease in lipotoxicity.

収録刊行物

• Diabetes

  Diabetes 50 (1), 131-138, 2001-01-01

  American Diabetes Association

キーワード

• Endocrinology, Diabetes and Metabolism
• Internal Medicine

詳細情報

• CRID: 1362544418798450560
• NII論文ID: 30026274384
• DOI: 10.2337/diabetes.50.1.131
• ISSN: 1939327X
• ISSN: 00121797
• ISSN: http://id.crossref.org/issn/00121797
• Web Site: https://journals.org/diabetes/diabetes/article-pdf/50/1/131/365873/0500131.pdf
• Web Site: https://diabetesjournals.org/diabetes/article-pdf/50/1/131/365873/0500131.pdf
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