Mechanism of action of sulfonylureas is ?

Ans. is 'a' i.e., Insulin release Sulfonylureas act by Sulfonylurease provoke a brisk release of insulin from pancreas. They act on the so called "Sulfonylurea receptors" (SUR1) on pancreatic b-cell membrane - cause depolarization by reducing conductance of ATP sensitive K+ channels. This enhances influx of Ca+2 - degranulation. They do not cause hypoglycemia in pancreatectomized animals and type 1 diabetes (Presence of at least 30% of functional b-cells in essential for their action). A minor action reducing glucagon secretion by increasing insulin and somatostatin release has been demonstrated. Extrahepatic action On chronic administration they sensitize the target cells (especially the liver) to the action of insulin. On chronic administration their action on pancrease (to release insuline) declines due to down regulation of sulfonylurea receptors. But glycemic control is maintained due to extrahepatic action.