Bumetanide reduces insulin release by a direct effect on the pancreatic β-cells

Abstract

The effect of the loop diuretic bumetanide on glucose-induced insulin release, 45Ca 2+ uptake, 36Cl − fluxes and 86Rb + (K + analogue) efflux was tested in isolated β-cell-rich mouse pancreatic islets. Low concentrations of bumetanide (0.1–10 μM) reduced glucose-induced insulin release as well as 45Ca 2+ uptake. High concentrations (0.5–1) mM) augmented glucose-induced insulin release and an intermediate concentration (100 μM) had no effect. Bumetanide (0.01–1 mM) reduced the islet accumulation of 36Cl −. The net efflux of 36Cl − in the presence of 20 mM D-glucose was reduced by a concentration (10 μM) that lowered glucose-induced insulin release. Bumetanide (10 μM) did not affect the rate coefficient for 36Cl − efflux, which suggests that chloride permeability is not affected. Bumetanide (10 μM) reduced 86Rb + efflux from preloaded islets. The data show that bumetanide reduces insulin release by a direct effect on pancreatic β-cells and suggest that this may be due to reduced chloide accumulation by a Na +, K +, Cl − co-transport system. It is suggested that the reduced chloride level is responsible for the decrease in glucose-induced chloride efflux and insulin release.