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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Palmitate-induced beta-cell dysfunction is associated with excessive NO production and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms.

Author

  • Sandra Meidute Abaraviciene
  • Ingmar Lundquist
  • Juris Galvanovskis
  • Erik Flodgren
  • Björn Olde
  • S Albert Salehi

Summary, in English

BACKGROUND: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgamma agonistic thiazolidinedione, rosiglitazone. PRINCIPAL FINDINGS: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and increased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. CONCLUSION: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes.

Department/s

  • Islet cell physiology
  • Medicine, Lund
  • Section II

Publishing year

2008

Language

English

Publication/Series

PLoS ONE

Volume

3

Issue

5

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Other Clinical Medicine
  • Endocrinology and Diabetes

Status

Published

Research group

  • Islet cell physiology

ISBN/ISSN/Other

  • ISSN: 1932-6203