Disappearance of glibenclamide-induced hypoglycemia in Wistar-Kyoto rats.

The aim of the present study is to investigate difference in sensitivity to glibenclamide, a sulfonylurea oral antidiabetic agent, among Wistar rats, Spontaneously Hypertensive rats (SHR/Izm) and Wistar-Kyoto rats (WKY/Izm). We examined the effect of glibenclamide on blood levels of glucose and insulin in these rat strains. Under anesthesia with pentobarbital sodium (50 mg/kg, i.p.), blood samples were collected before and 5—120 min after administration of glibenclamide (10 mg/kg, i.p.). Blood levels of glucose and insulin in each sample were measured by glucose oxidase method and radioimmunoassay, respectively. In 8 week-old rats of all strains tested, blood levels of glucose were decreased by glibenclamide. In 12—20-week-old rats, although blood levels of glucose in Wistar and SHR/Izm were decreased after glibenclamide administration, those of WKY/Izm were not decreased. In rats of this age, time-course and extent of increases in blood insulin levels observed after administration of glibenclamide in WKY/Izm was almost the same as that of SHR/Izm, however, smaller than that of Wistar. Both insulin secretions induced via inactivation of ATP-sensitive K+ channel and sensitivity of pancreatic β-cells to insulin seems to be decreased in WKY/Izm after 12 weeks of age. This phenomenon may explain the mechanism of glucose intolerance previously reported in WKY/Izm.