title: Inhibition by hydrochlorothiazide of insulin release and calcium influx in mouse pancreatic beta-cells.
abstract: 1. The effect of hydrochlorothiazide on insulin release, 36Cl- fluxes and 45Ca2+ uptake was tested in beta-cell-rich mouse pancreatic islets. 2. At high glucose concentrations (10 and 20 mmol l-1), low concentrations of hydrochlorothiazide (0.1-1.0 mumol 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 mumol l-1). 4. Glucose-stimulated 45Ca2+ uptake was significantly reduced by hydrochlorothiazide (1-10 mumol 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 beta-cells. The inhibition is not mediated by reduced chloride fluxes but may rather be caused by inhibition of calcium uptake.
authors.affiliation: Department of Histology and Cell Biology, University of Umeå, Sweden.
authors.forename: P E
authors.initials: PE
authors.lastname: Sandström
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D017136:Ion Transport / Q000187:drug effects; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D012964:Sodium / Q000378:metabolism
chemical_list: D002712:Chlorides; D007328:Insulin; D006852:Hydrochlorothiazide; D012964:Sodium; D002118:Calcium