Effects of Zn2+ on glucose-induced electrical activity and insulin release from mouse pancreatic islets.
The effects of Zn2+ and CO2+ on glucose-induced beta-cell electrical activity and on insulin release from microdissected mouse pancreatic islets were studied. In 11 mM glucose the electrical activity is characterized by a burst pattern with a bimodal distribution of spike amplitudes along the plateau phase. Zn2+ at 0.05 mM induced a reduction in the number of spikes during the bursts and preferentially blocked the large action potentials. Zn2+ at 0.1 mM and CO2+ at 1.0 mM completely inhibited the electrical activity in response to glucose. Zn2+ inhibition of electrical activity was poorly reversible, whereas CO2+ inhibition was rapidly and completely reversible. Zn2+ and CO2+ inhibited the glucose-stimulated insulin release from microdissected perifused islets. Half-maximal inhibition occurred at about 0.3 mM for both metals. Zn2+ also inhibited K+-induced insulin release in the absence of glucose, indicating that Zn2+ inhibition does not involve glucose metabolism. It is proposed that Zn2+ blocks the voltage-gated Ca2+ channels in pancreatic beta-cells.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002712:Chlorides; D003035:Cobalt / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds
D002712:Chlorides; D007328:Insulin; D017967:Zinc Compounds; D003035:Cobalt; C016837:zinc chloride; C018021:cobaltous chloride; D005947:Glucose; D015032:Zinc