The Effect of Chronic α-Glycosidase Inhibition on Diabetic Nephropathy in the db/db Mouse

Acarbose, a complex oligosaccharide, is a potent competitive inhibitor of sucrase and decreases postprandial hyperglycemia when administered with food. To evaluate its potential for metabolic control and prevention of diabetic nephropathy, groups of gentically diabetic mice (C57 BLKsJ db/db) were treated with Acarbose for 10 wk. Control mice received normal chow and experimental groups were given Acarbose prepared as a drug-food mixture in doses of 10, 20, and 40 mg/100 g of food. Acarbose did not influence fasting blood glucose, food intake, or the normal development of obesity in the mice. Urinary glucose excretion and glycosylated hemoglobin was significantly reduced in animals receiving high-dose Acarbose (40 mg/100 g food). Immunopathologic examination of the kidneys showed a dose-dependent decrease in glomerular mesangial immunoglobulin deposition. By light microscopy, glomerular mesangial thickening was significantly reduced in the group receiving high-dose Acarbose (40 mg/100 g food). To the extent that Acarbose improves metabolic control in the db/db mouse, chronic treatment with this agent produces a dose-dependent amelioration of diabetic nephropathy. Alphaglycosidase inhibition may be a useful adjunctive therapy for blood glucose control in diabetes mellitus.