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Chronic exposure to tolbutamide and glibenclamide impairs insulin secretion but not transcription of K-ATP channel components

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Ball, AJ, McCluskey, Janie, Flatt, Peter and McClenaghan, Neville (2004) Chronic exposure to tolbutamide and glibenclamide impairs insulin secretion but not transcription of K-ATP channel components. PHARMACOLOGICAL RESEARCH, 50 (1). pp. 41-46. [Journal article]

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DOI: 10.1016/j.phrs.2003.12.001


Clonal insulin-secreting BRIN-BD11 cells were used to examine effects of chronic 72-144 h exposure to the sulphonylureas tolbutamide and glibenclamide on insulin release, cellular insulin content, and mRNA levels of the Kir6.2 and SUR1 subunits of the beta-cell K-ATP channel. Chronic exposure for 72-144 It to 5-100 muM tolbutamide and glibenclamide resulted in a time- and concentration-dependent irreversible decline in sulphonylurea-induced insulin secretion. In contrast, the decline in cellular insulin content induced by chronic exposure to high concentrations of sulphonylureas was readily reversible. Chronic exposure to tolbutamide or glibenclamide had no effect upon transcription of the Kir6.2 or SUR1 subunits of the pancreatic beta-cell K-ATP channel. Whilst further studies are required to understand the precise nature of the chronic interactions of sulphonylurea with the insulin exocytotic mechanism, these observations may partially explain the well-known progressive failure of sulphonylurea therapy in type 2 diabetes. (C) 2003 Elsevier Ltd. All rights reserved.

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
Built Environment Research Institute
Biomedical Sciences Research Institute > Diabetes
Built Environment Research Institute > Centre for Research on Property and Planning (RPP)
ID Code:3019
Deposited By:Professor Peter Flatt
Deposited On:14 Jan 2010 15:42
Last Modified:15 Jun 2011 11:10

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