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

Abstract

1 The effect of hydrochlorothiazide on insulin release, ³⁶Cl⁻ fluxes and ⁴⁵Ca²⁺ uptake was tested in β-cell-rich mouse pancreatic islets. 2 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. 3 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). 4 Glucose-stimulated ⁴⁵Ca²⁺ uptake was significantly reduced by hydrochlorothiazide (1–10 μmol l⁻¹). 5 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.