Effect of perchlorate on calcium uptake and insulin secretion in mouse pancreatic islets

• Published in: Biochemical journal Vol. 248; no. 1; pp. 109 - 115
• Main Author: Sehlin, J
• Format: Journal Article
• Language: English
• Published: England 15.11.1987
• Subjects: Animals; calcium; Calcium - metabolism; Drug Synergism; Glucose - pharmacology; Glyburide - pharmacology; In Vitro Techniques; Insulin - metabolism; Insulin Secretion; islets of Langerhans; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Mannoheptulose - pharmacology; Mice; Mice, Obese; perchlorate; Perchlorates - pharmacology; Potassium - pharmacology; Sodium Compounds; Trichloroacetic Acid - pharmacology
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj2480109

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.