Effect of perchlorate on calcium uptake and insulin secretion in mouse pancreatic islets.
Microdissected beta-cell-rich pancreatic islets of non-inbred ob/ob mice were used in studies of how perchlorate (CIO4-) affects stimulus-secretion coupling in beta-cells. CIO4- at 16 mM potentiated D-glucose-induced insulin release, without inducing secretion at non-stimulatory glucose concentrations. The potentiation mainly applied to the first phase of stimulated insulin release. In the presence of 20 mM-glucose, the half-maximum effect of CIO4- was reached at 5.5 mM and maximum effect at 12 mM of the anion. The potentiation was reversible and inhibitable by D-mannoheptulose (20 mM) or Ca2+ deficiency. CIO4- at 1-8 mM did not affect glucose oxidation. The effects on secretion were paralleled by a potentiation of glucose-induced 45Ca2+ influx during 3 min. K+-induced insulin secretion and 45Ca2+ uptake were potentiated by 8-16 mM-CIO4-. The spontaneous inactivation of K+-induced (20.9 mM-K+) insulin release was delayed by 8 mM-CIO4-. The anion potentiated the 45Ca2+ uptake induced by glibenclamide, which is known to depolarize the beta-cell. Insulin release was not affected by 1-10 mM-trichloroacetate. It is suggested that CIO4- stimulates the beta-cell by affecting the gating of voltage-controlled Ca2+ channels.
Sehlin
J
J
Department of Histology and Cell Biology, University of Umeå, Sweden.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008356:Mannoheptulose / Q000494:pharmacology; D051379:Mice; D008820:Mice, Obese; D010472:Perchlorates / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D017670:Sodium Compounds; D014238:Trichloroacetic Acid / Q000494:pharmacology
D007328:Insulin; D010472:Perchlorates; D017670:Sodium Compounds; D014238:Trichloroacetic Acid; D008356:Mannoheptulose; C031068:sodium perchlorate; D005947:Glucose; D011188:Potassium; D005905:Glyburide; D002118:Calcium