Altered expression of muscle glucose transporter GLUT-4 in diabetic fatty Zucker rats (ZDF/Drt-fa).
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.
Friedman
J E
JE
Department of Biochemistry, School of Medicine, East Carolina University, Greenville, North Carolina 27858.
de Venté
J E
JE
Peterson
R G
RG
Dohm
G L
GL
D020909:Acarbose; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014312:Trisaccharides / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D014312:Trisaccharides; D020909:Acarbose