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Modulation of the insulinotropic action of glibenclamide and glimepiride by nutrient secretagogues in pancreatic islets from normoglycemic and hyperglycemic rats.

par Malaisse, Willy ;Lebrun, Philippe ;Sener, Abdullah
Référence Biochemical pharmacology, 45, 9, page (1845-1849)
Publication Publié, 1993-05

Article révisé par les pairs

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Résumé :

In perifused pancreatic islets from euglycemic rats, the secretory response to either glibenclamide or glimepiride (1.0 microM each) increases as a function of the concentration of D-glucose (2.8-16.7 mM) present in the perifusion medium. On the contrary, the sulfonylurea-induced increment in 45Ca efflux from prelabeled islets decreases at increasing concentrations of the hexose. Neither glibenclamide nor glimepiride affect D-glucose metabolism in isolated islets, as judged from the production of 3HOH from D-[5-3H]glucose or the generation of 14CO2, as well as 14C-labeled amino acids and acidic metabolites, from D-[3,4-14C]glucose, D-[2-14C]glucose and D-[6-14C]glucose. The insulinotropic action of the hypoglycemic sulfonylureas is not impaired in islets prepared from rats infused for 48 hr with a hypertonic solution of D-glucose. The dimethyl ester of succinic acid is more efficient than D-glucose in supporting the insulin-releasing effect of glibenclamide or glimepiride. Thus, although the insulinotropic action of hypoglycemic sulfonylureas appears unaffected in a model of B-cell glucotoxicity, a potentiation of their secretory effects might be expected, in non-insulin-dependent diabetes, from the combined administration of succinic acid methyl ester.