Ulster University Logo

Ulster Institutional Repository

Effects of metformin on BRIN-BD11 beta-cell insulin secretory desensitization induced by prolonged exposure to sulphonylureas

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Irwin, Nigel, McKinney, J. M., Bailey, C. J., Flatt, Peter and McClenaghan, Neville (2010) Effects of metformin on BRIN-BD11 beta-cell insulin secretory desensitization induced by prolonged exposure to sulphonylureas. DIABETES OBESITY & METABOLISM, 12 (12). pp. 1066-1071. [Journal article]

Full text not available from this repository.

DOI: 10.1111/j.1463-1326.2010.01294.x

Abstract

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.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:16590
Deposited By:Dr Nigel Irwin
Deposited On:08 Dec 2010 11:56
Last Modified:19 Nov 2012 15:41

Repository Staff Only: item control page