Inhibition by hydrochlorothiazide of insulin release and calcium influx in mouse pancreatic β‐cells

Abstract

The effect of hydrochlorothiazide on insulin release, 36Cl− fluxes and 45Ca2+ uptake was tested in β‐cell‐rich mouse pancreatic islets. At high glucose concentrations (10 and 20 mmol l−1), low concentrations of hydrochlorothiazide (0.1–1.0 μmol l−1) reduced insulin release by 22–42%. At lower glucose concentrations (3–8.5 mmol l−1) insulin release was not affected by the drug. Neither short‐term influx (3 min) nor net accumulation (60 min) of 36Cl− in the islets was affected by hydrochlorothiazide (0.1–500 μmol l−1). Glucose‐stimulated 45Ca2+ uptake was significantly reduced by hydrochlorothiazide (1–10 μmol l−1). The data suggest that the diabetogenic effect of hydrochlorothiazide, at least in part, can be mediated by direct inhibition of insulin release from the pancreatic β‐cells. The inhibition is not mediated by reduced chloride fluxes but may rather be caused by inhibition of calcium uptake. 1993 British Pharmacological Society