Miglitol (BAY m 1099) treatment of diabetic hypothalamic-dietary obese rats improves islet response to glucose.

OBJECTIVE

The well-absorbed alpha-glucosidase inhibitor, miglitol (BAY m 1099), was included in the diets of hypothalamic-dietary obese diabetic rats to investigate its ability to improve glycemia and thereby reverse glucotoxic effects on islet secretory response.

RESEARCH METHODS AND PROCEDURES

Female rats received bilateral electrolytic lesions of the ventromedial hypothalamus and were fed high-fat, sucrose-supplemented diets until hyperinsulinemia and hyperglycemia were observed after 3 hours of food deprivation (nonfed). Diabetic animals were assigned to miglitol-treated (40 mg/100 g of diet) or untreated groups for 3 weeks; pancreatic islets were isolated for incubation experiments.

RESULTS

No differences in food intake, body weights, or nonfed plasma glucose or insulin levels were seen between treated and untreated diabetic rats. Islets isolated from untreated diabetic rats showed elevated basal insulin release and no insulin secretory response to an elevation in glucose concentration. In contrast, islets obtained from miglitol-treated rats showed more normal basal release and a significant insulin secretory response to glucose. Incubation of islets, obtained from normal control rats or untreated diabetic rats, in media containing miglitol at levels estimated to exist in plasma of treated rats had no effect on islet insulin secretory responses to glucose.

DISCUSSION

Islet secretory response was improved despite continued hyperglycemia and severe insulin resistance. Miglitol treatment may improve islet sensitivity to glucose either through effects on islet metabolism requiring prolonged exposure or by improvement in postmeal glycemia, despite persistent hyperglycemia.