The influence of K(+)-induced membrane depolarization on insulin secretion in islets of lean and obese (ob/ob) mice.
The present study was undertaken to determine whether factors that affect K+ permeability produce differences in insulin secretion in the islets of obese versus lean mice. At basal glucose (3 mM), the obese islets secreted more insulin for a given increment in depolarizing K+ concentration and responded to a wider range of K+ concentrations (5-45 mM) than the lean islets (5-25 mM). In contrast, the membrane potential changes induced by increments in pK+ were not significantly different in the two types of islets. The islets of lean and obese mice treated with pertussis toxin showed a qualitatively similar response to glucose and to epinephrine, but only the control and pertussis toxin treated obese islets responded to K+ depolarization when deprived of calcium. Abnormal responses to quinine and apamin were identified in the islets of obese mice. These findings show that the abnormal insulin secretory response of the obese islet is due, at least in part, to a defect independent of glucose metabolism. This is best explained by an altered sensitivity of voltage-dependent events, most likely the result of differential effects of an intracellular element acting on ATP-sensitive and Ca2(+)-activated K+ channels, both of which are implicated in membrane repolarization.
Department of Biochemistry, University of Ottawa, Ont., Canada.
L A
LA
Fournier
H M
HM
Heick
N
N
Bégin-Heick
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism*; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology*; D011803:Quinine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D010566:Virulence Factors, Bordetella; D001030:Apamin; D011803:Quinine; D037342:Pertussis Toxin; D005947:Glucose; D011188:Potassium; D002118:Calcium