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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2015: 2.710
Rank 142 out of 289 in category Biochemistry & Molecular Biology in the 2015 Thomson Reuters Journal Citation Report/Science Edition

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Online
ISSN
1437-4315
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Volume 391, Issue 12 (Dec 2010)

Issues

Acute and long-term effects of metformin on the function and insulin secretory responsiveness of clonal β-cells

Joan M. McKiney
  • SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK
/ Nigel Irwin
  • SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK
/ Peter R. Flatt
  • SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK
/ Clifford J. Bailey
  • School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK
/ Neville H. McClenaghan
  • SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, BT52 1SA, UK
Published Online: 2010-09-24 | DOI: https://doi.org/10.1515/bc.2010.139

Abstract

Functional effects of acute and prolonged (48 h) exposure to the biguanide drug metformin were examined in the clonal pancreatic β-cell line, BRIN-BD11. Effects of metformin on prolonged exposure to excessive increased concentrations of glucose and palmitic acid were also assessed. In acute 20-min incubations, 12.5–50 μm metformin did not alter basal (1.1 mm glucose) or glucose-stimulated (16.7 mm glucose) insulin secretion. However, higher concentrations of metformin (100–1000 μm) increased (1.3–1.5-fold; p<0.001) insulin release at basal glucose concentrations, but had no effect on glucose-stimulated insulin secretion. There were no apparent acute effects of metformin on intracellular Ca2+ concentrations, but metformin enhanced (p<0.05 to p<0.01) the acute insulinotropic actions of GIP and GLP-1. Exposure for 48 h to 200 μm metformin improved aspects of β-cell insulin secretory function, whereas these benefits were lost at 1 mm metformin. Prolonged glucotoxic and lipotoxic conditions impaired β-cell viability and insulin release in response to glucose and to a broad range of insulin secretagogues. Concomitant culture with 200 μm metformin partially reversed many of the adverse effects of prolonged glucotoxic conditions. However, there were no beneficial effects of metformin under prolonged culture with elevated concentrations of palmitic acid. The results suggest that metformin exerts direct effects on β-cell viability, function and survival that could contribute to the use of this agent in the treatment of type 2 diabetes.

Keywords: β-cell; desensitisation; hyperglycaemia; insulin secretion; metformin

About the article

Corresponding author


Received: 2010-07-21

Accepted: 2010-08-10

Published Online: 2010-09-24

Published in Print: 2010-12-01


Citation Information: Biological Chemistry, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/bc.2010.139. Export Citation

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S. S. Torekov, S. Madsbad, and J. J. Holst
Obesity Reviews, 2011, Volume 12, Number 8, Page 593
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N. Irwin, J. M. McKinney, C. J. Bailey, P. R. Flatt, and N. H. McClenaghan
Diabetes, Obesity and Metabolism, 2010, Volume 12, Number 12, Page 1066

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