INHIBITION OF K-SECRETION BY THE SULFONYLUREA, GLIMEPIRIDE, IN RELATION TO ITS MEMBRANE-BINDING IN PANCREATIC-ISLETS( CHANNELS AND STIMULATION OF INSULIN)

In isolated pancreatic islets of mice, the relationships between free glimepiride concentration and membrane binding or inhibition of ATP-se nsitive K+ channels were examined. Microsomal membrane binding and Kchannel inhibition were half-maximal at 0.7 and 0.3 nmol/l glimepiride , respectively. The corresponding concentrations for glibenclamide wer e 0.4 and 0.6 nmol/l. Administration of glimepiride (10 nmol/l) or gli benclamide (10 nmol/l) to isolated mouse islets perifused with albumin -containing media induced a slow increase in insulin secretion. The ki netics of the secretory responses to glimepiride and glibenclamide wer e identical. Determination of albumin binding revealed that the free g limepiride and glibenclamide concentrations applied in our investigati on were in the range of therapeutic serum concentrations of the free d rugs. It is concluded that the effects of glimepiride and glibenclamid e are very similar in mouse beta-cells.