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Investigation of the effects of sulfonylurea exposure on pancreatic beta cell metabolism

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

Brennan, Lorraine, Hewage, Chandralal, Malthouse, J. P. G., McClenaghan, Neville, Flatt, Peter and Newsholme, Philip (2006) Investigation of the effects of sulfonylurea exposure on pancreatic beta cell metabolism. FEBS JOURNAL, 273 (22). pp. 5160-5168. [Journal article]

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DOI: 10.1111/j.1742-4658.2006.05513.x

Abstract

Prolonged exposure of pancreatic beta cells to the sulfonylureas glibencamide and tolbutamide induces subsequent desensitization to the actions of these drugs. The precise mechanisms underlying this desensitization remain unknown, prompting the present study, which investigated the impact of prolonged sulfonylurea exposure on glucose and energy metabolism using clonal pancreatic BRIN-BD11 beta cells. Following prolonged exposure to tolbutamide, BRIN-BD11 beta cells were incubated in the presence of [U-C-13]glucose, and isotopomer analysis revealed that there was a change in the ratio of flux through pyruvate carboxylase (EC 6.4.1.1) and pyruvate dehydrogenase (EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4). Energy status in intact BRIN-BD11 cells was determined using P-31-NMR spectroscopy. Exposure to tolbutamide did not alter the nucleotide triphosphate levels. Collectively, data from the present study demonstrate that prolonged exposure of beta cells to tolbutamide results in changes in flux through key enzymes involved in glucose metabolism that, in turn, may impact on glucose-induced insulin secretion.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:2960
Deposited By:Professor Peter Flatt
Deposited On:17 Dec 2009 15:03
Last Modified:15 Jun 2011 11:10

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