[Mechanisms of action of peroral antidiabetics. Sulfonylurea preparations block the ATP-dependent potassium channels].
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.
Larsson
O
O
Rolf Lufts centrum för diabetesforskning, Karolinska institutet och Karolinska sjukhuset, Stockholm.
Kindmark
H
H
Bränström
R
R
Berggren
P O
PO
D000255:Adenosine Triphosphate / Q000502:physiology*; D000284:Administration, Oral; D049673:History, 20th Century; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000266:history / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D015221:Potassium Channels / Q000187:drug effects*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000266:history / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D000255:Adenosine Triphosphate