EFFECT OF TWO SULPHONYLUREAS ON THE DOSE KINETICS OF GLUCOSE – INDUCED INSULIN RELEASE IN NORMAL AND DIABETIC SUBJECTS

Abstract

The effect of two second generation sulphonylureas, gliquidone and glibenclamide, on insulin secretion has been studied in the basal state and in combination with glucose infusions in normal controls, patients with mild maturity-onset diabetes, and subjects with normal glucose tolerance but low insulin response. When injected intravenously, gliquidone caused rapid elevation of plasma insulin, peaking at 5 min in all groups, while glibenclamide induced a slow rise in insulin. Insulin response was somewhat smaller than normal in diabetics and low insulin responders. In all groups, 25 μg/kg glibenclamide and 200 μg/kg gliquidone were equipotent in generating an insulin response at the basal state. Equipotent amounts of sulphonylureas were combined with glucose infusions at three different dose levels. The glucose-insulin dose relationships, established by giving glucose alone, demonstrated curves that were flatter, and shifted to the right of the control in diabetics and low insulin responders, the changes being more marked in the former group. Addition of sulphonylurea induced a left shift in the dose-response relationships in controls and low insulin responders; under these conditions the effect of glibenclamide was more pronounced than that of gliquidone. The doseresponse relation for glucose-induced insulin release was completely normalized in low responders when sulphonylureas were added. In the group of mild diabetics, insulin response to glucose was enhanced by sulphonylureas only to a modest extent, the dose-response curves remaining grossly abnormal. It is concluded that, under acute experiments, sulphonylureas correct the deficient insulin response only in subjects with minimal abnormalities of the glucose tolerance; their effect in diabetics, even very mild ones, is marginal.