Furosemide reduces insulin release by inhibition of Cl- and Ca2+ fluxes in beta-cells.
The effect of furosemide on insulin release, glucose oxidation, 36Cl- fluxes, and 45Ca2+ uptake was studied in isolated, beta-cell-rich pancreatic islets from ob/ob mice. Low concentrations of furosemide (0.01-0.1 mM) reduced the glucose-induced insulin release, whereas high doses (1-10 mM) increased basal and glucose-induced release. Furosemide at concentrations that reduced glucose-induced insulin release (0.01-0.1 mM) did not affect the islet production of 14CO2 from D-[U-14C]glucose. The influx rate and equilibrium content of 36Cl- were reduced by furosemide, whereas the basal and glucose-stimulated 36Cl- efflux rates were unaffected. The glucose-induced (10 mM) uptake of 45Ca2+ was inhibited by furosemide. It is suggested that the diabetogenic action of furosemide may be due, at least in part, to direct inhibition of insulin release from the pancreatic beta-cells. This may be caused primarily by inhibition of an inwardly directed Cl- pump, leading to a reduced transmembrane electrochemical gradient for chloride in the beta-cells. This reduced gradient in combination with unaltered Cl- permeability may lead to decreased total outward Cl- transport, a factor associated with stimulated calcium uptake and insulin release.
Sandström
P E
PE
Department of Histology, University of Umeå, Sweden.
Sehlin
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002713:Chlorine / Q000378:metabolism*; D003864:Depression, Chemical; D005665:Furosemide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese
D007328:Insulin; D002713:Chlorine; D005665:Furosemide; D002118:Calcium