Interrelationship between chloride fluxes in pancreatic islets and insulin release.

The role of Cl- in the function of pancreatic beta-cells was studied by using islets of noninbred ob/ob mice. 36Cl- was rapidly taken up by islet cells; apparent isotope equilibrium was reached within 30 min. The apparent distribution ratio was 0.50--0.72 in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) medium and about 1.1 in Krebs-Henseleit medium. Uptake of 36Cl- was inhibited by 2,4-dinitrophenol, increased by ouabain, and not affected by omission of K+, Na+, or Ca2+. D-Glucose increased short-term uptake of 36Cl- but decreased the equilibrium content. Efflux of 36Cl- from prelabeled islets approached first-order kinetics with a half-life of about 5 min, was inhibited by 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonic acid or low temperature, was stimulated by D-glucose, D-mannose, or hydronium ion, and was unaffected by L-glucose or 3-O-methyl-D-glucose; D-manno-heptulose abolished the effect of D-glucose. Insulin secretion in response to D-glucose was reversibly inhibited in Cl- -deficient media. It is suggested that Cl- is nonpassively distributed across the beta-cell plasma membrane. D-Glucose-induced depolarization of beta-cells may partly be mediated by an increase of the Cl- permeability.