Bumetanide reduces insulin release by a direct effect on the pancreatic beta-cells.
The effect of the loop diuretic bumetanide on glucose-induced insulin release, 45Ca2+ uptake, 36Cl- fluxes and 86Rb+ (K+ analogue) efflux was tested in isolated beta-cell-rich mouse pancreatic islets. Low concentrations of bumetanide (0.1-10 microM) reduced glucose-induced insulin release as well as 45Ca2+ uptake. High concentrations (0.5-1 mM) augmented glucose-induced insulin release and an intermediate concentration (100 microM) 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 microM) that lowered glucose-induced insulin release. Bumetanide (10 microM) did not affect the rate coefficient for 36Cl- efflux, which suggests that chloride permeability is not affected. Bumetanide (10 microM) reduced 86Rb+ efflux from preloaded islets. The data show that bumetanide reduces insulin release by a direct effect on pancreatic beta-cells and suggest that this may be due to reduced chloride 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.
Sandström
P E
PE
Department of Histology and Cell Biology, University of Umeå, Sweden.
D000818:Animals; D002034:Bumetanide / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002132:Calcium Radioisotopes; D002712:Chlorides / Q000378:metabolism; D002713:Chlorine; D003864:Depression, Chemical; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011868:Radioisotopes; D012413:Rubidium / Q000378:metabolism; D012414:Rubidium Radioisotopes
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D002712:Chlorides; D007328:Insulin; D011868:Radioisotopes; D012414:Rubidium Radioisotopes; D002034:Bumetanide; D002713:Chlorine; D012413:Rubidium