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

Nigel Irwin, J. M. McKinney, C. J. Bailey, Neville McClenaghan, Peter Flatt

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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 mu M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 mu M) enhanced (p < 0.001) the acute insulinotropic action of GLP-1. Prolonged exposure to 6.25 mu M 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 mu M rosiglitazone. Culture with 6.25 mu M rosiglitazone further decreased acute insulin release under glucotoxic conditions. However, when insulin secretion was expressed as percentage cellular insulin content, rosiglitazone (6.25 mu M) 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.
LanguageEnglish
Pages244-249
JournalHORMONE AND METABOLIC RESEARCH
Volume43
Issue number4
DOIs
Publication statusPublished - Apr 2011

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rosiglitazone
PPAR gamma
Insulin
Thiazolidinediones
Cell Survival
Glucose
Glucagon-Like Peptide 1
Insulin-Secreting Cells
Hypoglycemic Agents
Alanine

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title = "Acute and Long-term Effects of Peroxisome Proliferator-activated Receptor-gamma Activation on the Function and Insulin Secretory Responsiveness of Clonal Beta-Cells",
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 mu M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 mu M) enhanced (p < 0.001) the acute insulinotropic action of GLP-1. Prolonged exposure to 6.25 mu M 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 mu M rosiglitazone. Culture with 6.25 mu M rosiglitazone further decreased acute insulin release under glucotoxic conditions. However, when insulin secretion was expressed as percentage cellular insulin content, rosiglitazone (6.25 mu M) 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.",
author = "Nigel Irwin and McKinney, {J. M.} and Bailey, {C. J.} and Neville McClenaghan and Peter Flatt",
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Acute and Long-term Effects of Peroxisome Proliferator-activated Receptor-gamma Activation on the Function and Insulin Secretory Responsiveness of Clonal Beta-Cells. / Irwin, Nigel; McKinney, J. M.; Bailey, C. J.; McClenaghan, Neville; Flatt, Peter.

In: HORMONE AND METABOLIC RESEARCH, Vol. 43, No. 4, 04.2011, p. 244-249.

Research output: Contribution to journalArticle

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T1 - Acute and Long-term Effects of Peroxisome Proliferator-activated Receptor-gamma Activation on the Function and Insulin Secretory Responsiveness of Clonal Beta-Cells

AU - Irwin, Nigel

AU - McKinney, J. M.

AU - Bailey, C. J.

AU - McClenaghan, Neville

AU - Flatt, Peter

PY - 2011/4

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AB - 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 mu M) did not alter basal or glucose-stimulated insulin secretion. However, rosiglitazone (6.25 mu M) enhanced (p < 0.001) the acute insulinotropic action of GLP-1. Prolonged exposure to 6.25 mu M 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 mu M rosiglitazone. Culture with 6.25 mu M rosiglitazone further decreased acute insulin release under glucotoxic conditions. However, when insulin secretion was expressed as percentage cellular insulin content, rosiglitazone (6.25 mu M) 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.

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DO - 10.1055/s-0030-1269897

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EP - 249

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JF - Hormone and Metabolic Research

SN - 0018-5043

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ER -