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Horm Metab Res 2011; 43(4): 244-249
DOI: 10.1055/s-0030-1269897
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Acute and Long-term Effects of Peroxisome Proliferator-activated Receptor-γ Activation on the Function and Insulin Secretory Responsiveness of Clonal Beta-Cells

N. Irwin1 , J. M. McKinney1 , C. J. Bailey2 , N. H. McClenaghan1 , P. R. Flatt1
  • 1SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine, Northern Ireland, UK
  • 2School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham, UK
Further Information

Publication History

received 04.10.2010

accepted 22.11.2010

Publication Date:
16 December 2010 (online)

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Abstract

Thiazolidinediones (TZDs) are used as antidiabetic therapy. The purpose of the present study was to examine whether the TZD rosiglitazone has direct actions on pancreatic beta-cells that contribute to its overall effects. Effects of acute and prolonged (48 h) exposure to rosiglitazone, as a model glitazone compound, were assessed in clonal pancreatic BRIN-BD11 beta-cells maintained in standard, glucotoxic and lipotoxic cultures. In acute 20-min incubations, rosiglitazone (0.2–100 μM) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 μM) enhanced (p<0.001) the acute insulinotropic action of GLP-1. Prolonged exposure to 6.25 μM rosiglitazone in standard media had no effect on cell viability or cellular insulin content, but slightly reduced the insulin secretory response to glucose and alanine (p<0.05). Prolonged (48 h) exposure to glucotoxic or lipotoxic conditions reduced beta-cell viability (p<0.05), cellular insulin content (p<0.001 and p<0.05, respectively), and insulin release in response to glucose and a range of secretagogues. The adverse effect of lipotoxicity on beta-cell viability was prevented by concomitant exposure to 6.25 μM rosiglitazone. Culture with 6.25 μM rosiglitazone further decreased acute insulin release under glucotoxic conditions. However, when insulin secretion was expressed as percentage cellular insulin content, rosiglitazone (6.25 μM) significantly improved many of the adverse effects of gluco- and lipotoxic conditions on insulin secretory responsiveness. The results suggest that despite decrease in cellular insulin content TZDs exert direct beneficial effects on beta-cell viability and function during gluco- or lipotoxicity.

Key words

insulin secretion - rosiglitazone - beta-cell - AMPK - PPAR-γ

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Correspondence

Dr. N. Irwin

SAAD Centre for Pharmacy and

Diabetes

University of Ulster

Coleraine

BT52 1SA Northern Ireland

UK

Phone: +44/2870/324 574

Fax: +44/2870/323 939

Email: n.irwin@ulster.ac.uk

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