Age-and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes

Deepak Jain, Ruchi Jain, Daniel Eberhard, Jan Eglinger, Marco Bugliani, Lorenzo Piemonti, Piero Marchetti, Eckhard Lammert

Research output: Contribution to journalArticle

Abstract

Elderly patients often suffer from multiple age-related diseases. Here we show that the expression of DJ-1, an antioxidant protein with reduced expression in the central nervous system of patients with Parkinson's disease, is reduced in pancreatic islets of patients with type 2 diabetes mellitus (T2DM). In contrast, under non-diabetic conditions, DJ-1 expression increases in mouse and human islets during aging. In mouse islets, we show that DJ-1 prevents an increase in reactive oxygen species levels as the mice age. This antioxidant function preserves mitochondrial integrity and physiology, prerequisites for glucose-stimulated insulin secretion. Accordingly, DJ-1-deficient mice develop glucose intolerance and reduced β cell area as they age or gain weight. Our data suggest that DJ-1 is more generally involved in age-and lifestyle-related human diseases and show for the first time that DJ-1 plays a key role in glucose homeostasis and might serve as a novel drug target for T2DM.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalJournal of Molecular Cell Biology
Volume4
Issue number4
DOIs
Publication statusPublished - Aug 2012

Keywords

  • diabetes
  • DJ-1
  • mitochondria
  • pancreatic islets

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology
  • Genetics

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