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• W1569794080 startingPage "2237" @default.
• W1569794080 abstract "Dantrolene is felt to inhibit the release of Ca2+ from vesicular stores but only in response to certain stimuli; the mechanism responsible for its effects is unclear. Since our recent studies implicated arachidonic acid and other polyunsaturated fatty acids in Ca2+ mobilization and insulin release from pancreatic islets, we have now examined the effect of dantrolene on fatty acid-induced 45Ca2+ efflux and insulin release. Dantrolene inhibited insulin secretion induced by exogenous unsaturated fatty acids as well as that caused by endogenous fatty acids (generated via the exogenous provision of pancreatic phospholipase A2, or by p-hydroxymercuribenzoic acid, which prevents the reacylation of free fatty acids). In contrast, the effects of 50 mM K+, 2mM BaCl2, 1 mM isobutylmethylxanthine or lyso-phosphatidylcholine were not impaired, suggesting that dantrolene does not inhibit nonspecifically the influx, mobilization or cellular effects of Ca2+, or poison exocytosis in general. However, dantrolene did reduce insulin secretion triggered by 12-O-tetradecanoylphorbol-13-acetate, mezerein or exogenous phospholipase C, all of which can activate protein kinase C; this inhibition was not accompanied by alterations in 45Ca2+ efflux. Furthermore, the 45Ca2+ efflux induced by phospholipase A2 or p-hydroxymercuribenzoic acid was not reduced by dantrolene. We conclude that the insulin secretion stimulated by unsaturated fatty acids involves two effects (one on Ca2+ fluxes, and one independent of Ca2+ mobilization). Dantrolene, in turn, may selectively probe such fatty acid-dependent insulin release; its inhibitory effect is predominantly, if not totally, independent of effects on Ca2+ fluxes, and may involve the inhibition of the effects of protein kinase C on exocytosis." @default.
• W1569794080 created "2016-06-24" @default.
• W1569794080 creator A5089866905 @default.
• W1569794080 date "1988-06-01" @default.
• W1569794080 modified "2023-09-25" @default.
• W1569794080 title "Dantrolene-induced inhibition of insulin release" @default.
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• W1569794080 doi "https://doi.org/10.1016/0006-2952(88)90587-4" @default.
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