期刊
DIABETES OBESITY & METABOLISM
卷 12, 期 12, 页码 1066-1071出版社
WILEY
DOI: 10.1111/j.1463-1326.2010.01294.x
关键词
clonal pancreatic beta-cell; desensitization; insulin release; metformin; sulphonylurea
Methods: Acute and prolonged (18 h) effects of exposure to tolbutamide and glibenclamide alone, or in the presence of metformin, were examined in insulin-secreting BRIN-BD11 cells. Results: In acute 20 min incubations at 1.1 mM glucose, metformin increased (1.2-1.7-fold; p < 0.001) the insulin-releasing actions of tolbutamide and glibenclamide. At 16.7 mM glucose, metformin significantly enhanced glibenclamide-induced insulin release at all concentrations (50-400 mu M) examined, but tolbutamide-stimulated insulin secretion was only augmented at higher concentrations (300-400 mu M). Exposure for 18 h to 100 mu M tolbutamide or glibenclamide significantly impaired insulin release in response to glucose and a broad range of insulin secretagogues. Concomitant culture with metformin (200 mu M) prevented or partially reversed many of the adverse effects on K-ATP channel dependent and independent insulinotropic pathways. Beneficial effects of metformin were also observed in cells exposed to glibenclamide for 18 h with significant improvements in the insulin secretory responsiveness to alanine, GLP-1 and sulphonylureas. The decrease of viable cell numbers observed with glibenclamide was reversed by co-culture with metformin, but cellular insulin content was depressed. Conclusions: The results suggest that metformin can prevent the aspects of sulphonylurea-induced beta-cell desensitization.
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