Inhibition of K+ channels and stimulation of insulin secretion by the sulfonylurea, glimepiride, in relation to its membrane binding in pancreatic islets.

In isolated pancreatic islets of mice, the relationships between free glimepiride concentration and membrane binding or inhibition of ATP-sensitive K+ channels were examined. Microsomal membrane binding and K+ channel inhibition were half-maximal at 0.7 and 0.3 nmol/l glimepiride, respectively. The corresponding concentrations for glibenclamide were 0.4 and 0.6 nmol/l. Administration of glimepiride (10 nmol/l) or glibenclamide (10 nmol/l) to isolated mouse islets perifused with albumin-containing media induced a slow increase in insulin secretion. The kinetics of the secretory responses to glimepiride and glibenclamide were identical. Determination of albumin binding revealed that the free glimepiride and glibenclamide concentrations applied in our investigation were in the range of therapeutic serum concentrations of the free drugs. It is concluded that the effects of glimepiride and glibenclamide are very similar in mouse beta-cells.