Altered expression of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa)

• Published in: The American journal of physiology Vol. 261; no. 6 Pt 1; p. E782
• Main Authors: Friedman, J E, de Venté, J E, Peterson, R G, Dohm, G L
• Format: Journal Article
• Language: English
• Published: United States 01.12.1991
• Subjects: Acarbose; Animals; Blood Glucose - metabolism; Blotting, Western; Body Weight; Diabetes Mellitus, Experimental - metabolism; Down-Regulation; Gene Expression Regulation; Hypoglycemic Agents - pharmacology; Male; Monosaccharide Transport Proteins - genetics; Monosaccharide Transport Proteins - metabolism; Muscles - metabolism; Obesity - metabolism; Rats; Rats, Zucker; Trisaccharides - pharmacology
• ISSN: 0002-9513; 2163-5773
• DOI: 10.1152/ajpendo.1991.261.6.e782

We examined GLUT-4 glucose transporter protein and mRNA in muscle tissue from a new rodent model of non-insulin-dependent diabetes mellitus (NIDDM), the male obese Zucker diabetic fatty (ZDF) rat [ZDF/Drt-fa(F10)]. We also determined whether prevention of hyperglycemia might affect GLUT-4 expression by feeding the intestinal alpha-glucosidase inhibitor acarbose (40 mg/100 g diet) in the diet of male ZDF rats for 19 wk, starting at least 1 wk before the onset of diabetes. Fasting glucose was four- to sixfold greater in diabetic ZDF rats (24.1 +/- 6.7 mM) compared with lean or obese nondiabetic rats. Fasting insulin in diabetic ZDF rats (0.5 +/- 0.1 ng/ml) was similar to lean rats (0.4 +/- 0.1) but greatly reduced compared with obese nondiabetic rats (18.7 +/- 4.0 ng/ml). Acarbose treatment significantly reduced fasting glucose levels to 13.4 +/- 1.4 mM, while insulin levels increased to 1.6 +/- 0.3 ng/ml. GLUT-4 protein levels in diabetic ZDF rats were reduced approximately 40% in red quadriceps and mixed gastrocnemius muscles but were unchanged in white quadriceps muscle. Acarbose treatment was associated with a twofold increase in GLUT-4 protein and mRNA in mixed gastrocnemius muscle. These data indicate that, in this obese model of NIDDM without hyperinsulinemia, there is reduced muscle GLUT-4 protein in red but not white muscle fiber types. The decrease in muscle GLUT-4 expression in this model of NIDDM can be prevented by acarbose treatment, which reduces hyperglycemia and increases beta-cell responsiveness.