Modulation of dihydropyridine-sensitive Ca2+ channels by glucose metabolism in mouse pancreatic beta-cells.
Glucose stimulates insulin secretion from the pancreatic beta-cell by increasing the cytosolic calcium concentration. It is believed that this increment results mainly from Ca2+ influx through dihydropyridine-sensitive calcium channels because insulin secretion is abolished by dihydropyridine antagonists and is potentiated by dihydropyridine agonists. Glucose may influence Ca2+ influx through these channels in two ways: either by regulating the beta-cell membrane potential or by biochemical modulation of the channel itself. The former mechanism is well established. Glucose metabolism, by closing ATP-sensitive K+ channels, depolarizes the beta-cell membrane and initiates Ca2+-dependent electrical activity, with higher glucose concentrations further increasing Ca2+ influx by raising the frequency of action potentials. We show here that glucose metabolism also increases calcium influx directly, by modulating the activity of dihydropyridine-sensitive Ca2+ channels.
Smith
P A
PA
University Laboratory of Physiology, Oxford, UK.
Rorsman
P
P
Ashcroft
F M
FM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology; D004553:Electric Conductivity; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D051379:Mice
D015220:Calcium Channels; D004095:Dihydropyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D005947:Glucose; D002118:Calcium