THERAPEUTIC CONCENTRATIONS OF TOLBUTAMIDE, GLIBENCLAMIDE, GLICLAZIDE AND GLIQUIDONE AT DIFFERENT GLUCOSE-LEVELS - INVITRO EFFECTS ON PANCREATIC A-CELL AND B-CELL FUNCTION

In the classical model of isolated perfused rat pancreas four commonly used sulfonylureas - tolbutamide, glibenclamide, gliquidone and gliclazide - were investigated at therapeutical concentrations at three different glucose levels (with 0, 2.22 and 5 mmol/l glucose surrounding) and in the presence of a metabolic stimulus with glucose at 8.33 mmol/l. All the sulfonylureas stimulated the B-cell function. Tolbutamide, gliquidone and gliclazide produced a prompt biphasic hormone release while glibenclamide induced a delayed monophasic insulin secretion. In all cases the amount of insulin released depended on the metabolic condition. As the environmental glucose levels fell, the sulfonylureas' stimulatory effect on the B-cell function decreased. At the therapeutical concentrations we tested, no sulfonylurea influenced A-cell activity whether directly or indirectly via an insulin-mediated paracrine inhibition of glucagon release.