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Susceptibility to fatty acid-induced β-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: A potential link between β-cell lipotoxicity and islet inflammation
Endocrinology
  • Christine Tang, University of Toronto
  • Anthony E. Naassan, University of Toronto
  • Astrid Chamson-Reig, Western University
  • Khajag Koulajian, University of Toronto
  • Tracy T. Goh, University of Toronto
  • Frederick Yoon, University of Toronto
  • Andrei I. Oprescu, University of Toronto
  • Husam Ghanim, University at Buffalo, The State University of New York
  • Gary F. Lewis, University of Toronto
  • Paresh Dandona, University at Buffalo, The State University of New York
  • Marc Y. Donath, UniversitatsSpital Zurich
  • Jan A. Ehses, BC Children's Hospital Research Institute
  • Edith Arany, Western University
  • Adria Giacca, University of Toronto
Document Type
Article
Publication Date
1-1-2013
URL with Digital Object Identifier
10.1210/en.2012-1720
Disciplines
Abstract

β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity maybe synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ∼2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased β-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced β-cell dysfunction in the BB rat, which suggests a link between β-cell lipotoxicity and islet inflammation. Copyright © 2013 by The Endocrine Society.

Citation Information
Christine Tang, Anthony E. Naassan, Astrid Chamson-Reig, Khajag Koulajian, et al.. "Susceptibility to fatty acid-induced β-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: A potential link between β-cell lipotoxicity and islet inflammation" Endocrinology Vol. 154 Iss. 1 (2013) p. 89 - 101
Available at: http://works.bepress.com/edith-arany/11/