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The effects of various stimulants of insulin release on cytosolic free Ca2+, [Ca2+]i, in dispersed and cultured pancreatic beta-cells from ob/ob-mice were studied using the indicator quin-2, which in itself has only slight effects on the glucose-induced insulin release and the metabolism of the sugar. The resting [Ca2+]i was 158 +/- 7 nM. After increasing glucose to 20 mM there was a lag-period of 1-2 min before [Ca2+]i gradually rose, reaching a new plateau 60% higher after 5-6 min. Increasing intracellular cyclic AMP by adding forskolin did not further increase [Ca2+]i; on the contrary there was a slight temporary reduction despite a doubling of insulin secretion. The maintenance of the beta-cell function was evident from a marked increase of cytosolic [Ca2+]i after depolarization evoked by high extracellular K+. Also dibutyryl cyclic AMP and theophylline lacked the ability to raise [Ca2+]i beyond that obtained by glucose. The results suggest that cyclic AMP potentiates glucose-induced insulin release by sensitizing the secretory machinery to changes of [Ca2+]i rather than by increasing the cytosolic concentration of the ion.

Original publication

DOI

10.1111/j.1748-1716.1985.tb07766.x

Type

Journal article

Journal

Acta Physiol Scand

Publication Date

12/1985

Volume

125

Pages

639 - 647

Keywords

Animals, Calcium, Cells, Cultured, Colforsin, Cyclic AMP, Cytosol, Female, Fluorescent Antibody Technique, Glucose, Insulin, Islets of Langerhans, Male, Mice, Mice, Obese, Oxidation-Reduction