Glucose intolerance and pancreatic β-cell dysfunction in the anorectic anx/anxmouse

Charlotte Lindfors, Abram Katz, Lars Selander, Jeanette E. Johansen, Giulia Marconi, Martin Schalling, Tomas Hökfelt, Per Olof Berggren, Sergei Zaitsev, Ida A K Nilsson

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Inflammation and impaired mitochondrial oxidative phosphorylation are considered key players in the development of several metabolic disorders, including diabetes. We have previously shown inflammation and mitochondrial dysfunction in the hypothalamus of an animal model for anorexia, the anx/anx mouse. Moreover, increased incidence of eating disorders, e.g., anorexia nervosa, has been observed in diabetic individuals. In the present investigation we evaluated whether impaired mitochondrial phosphorylation and inflammation also occur in endocrine pancreas of anorectic mice, and if glucose homeostasis is disturbed. We show that anx/anx mice exhibit marked glucose intolerance associated with reduced insulin release following an intraperitoneal injection of glucose. In contrast, insulin release from isolated anx/anx islets is increased after stimulation with glucose or KCl. In isolated anx/anx islets there is a strong downregulation of the mitochondrial complex I (CI) assembly factor, NADH dehydrogenase (ubiquinone) 1α subcomplex, assembly factor 1 (Ndufaf1), and a reduced CI activity. In addition, we show elevated concentrations of free fatty acids (FFAs) in anx/anx serum and increased macrophage infiltration (indicative of inflammation) in anx/anx islets. However, isolated islets from anx/anx mice cultured in the absence of FFAs do not exhibit increased inflammation. We conclude that the phenotype of the endocrine pancreas of the anx/anx mouse is characterized by increased levels of circulating FFAs, as well as inflammation, which can inhibit insulin secretion in vivo. The anx/anx mouse may represent a useful tool for studying molecular mechanisms underlying the association between diabetes and eating disorders.

Original languageEnglish (US)
Pages (from-to)E418-E427
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume309
Issue number4
DOIs
StatePublished - Aug 18 2015
Externally publishedYes

Keywords

  • Anorexia
  • Free fatty acids
  • Insulin
  • Macrophages
  • Mitochondrial dysfunction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism

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    Lindfors, C., Katz, A., Selander, L., Johansen, J. E., Marconi, G., Schalling, M., Hökfelt, T., Berggren, P. O., Zaitsev, S., & Nilsson, I. A. K. (2015). Glucose intolerance and pancreatic β-cell dysfunction in the anorectic anx/anxmouse. American Journal of Physiology - Endocrinology and Metabolism, 309(4), E418-E427. https://doi.org/10.1152/ajpendo.00081.2015