ATP-sensitive potassium channels (KATP) are the
ion channels which are closely associated with cellular metabolism. A number of chemical compounds which block KATP facilitate the release of
hormones or
neuropeptides. For example, KATP-blocking agents such as
antidiabetic sulfonylureas and
imidazolines stimulate insulin secretion from pancreatic beta-cells by decreasing KATP activity. On the other hand, so-called
potassium channel openers, KATP-activating drugs which constitute a chemically diverse group of compounds, inhibit
growth hormone secretion from anterior pituitary cells and release of gamma-aminobutylic
acid from substantia nigra. Several endogenous substances also modulate release of
hormone or
neuropeptide by affecting KATP activity.
Acetylcholine and
histamine stimulate the release of endothelium-derived hyperpolarizing factor, which activates KATP in the plasma membrane of vascular smooth muscle cells. Both
galanin and
somatostatin inhibit
insulin release from pancreatic beta-cells by opening KATP through the activation of
G-protein.
Glucagon-like peptide-1[7-36], which stimulates insulin secretion by indirectly blocking KATP in beta-cells, shows
antidiabetic effects in patients with
non-insulin-dependent diabetes mellitus. Endosulphine, an endogenous inhibitor of KATP, stimulates insulin secretion from pancreatic beta-cells. Accumulating knowledge of the modulation and function of KATP would help our understanding of the regulation and physiological role of
hormones and
neuropeptides.