Mechanisms of action of peroral antidiabetics. Sulfonylurea preparations block the ATP-dependent potassium channels
Larsson, O.; Kindmark, H.; Bränström, R.; Berggren, P.O.
Lakartidningen 94(48): 4473-4477
1997
ISSN/ISBN: 0023-7205 PMID: 9424548 Document Number: 480873
Although hypoglycaemic sulphonylureas have been used to treat non-insulin-dependent diabetes mellitus (NIDDM) for the past forty years, their mechanisms of action at the molecular level have only recently been elucidated. A combination of electrophysiological and molecular biological techniques showed the target of sulphonylureas to be a sulphonylurea receptor (SUR1) and potassium channel (Kir6.2) complex. Together, these two proteins form the ATP-dependent potassium (KATP) channel occurring in insulin-secreting cells. An increase in the blood glucose level triggers a chain of events in insulin-secreting cells and K(ATP) channel closure which is a prerequisite for insulin secretion. In NIDDM, however, an increase in blood glucose fails to close the K(ATP) channel satisfactorily, but this can be remedied by the administration of sulphonylureas.