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

作者：Jain Deepak; Jain Ruchi; Eberhard Daniel; Eglinger Jan; Bugliani Marco; Piemonti Lorenzo; Marchetti Piero; Lammert Eckhard^*

来源：Journal of Molecular Cell Biology, 2012, 4(4): 221-230.

DOI：10.1093/jmcb/mjs025

• diabetes
• pancreatic islets
• DJ-1
• mitochondria

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 Parkinsons 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 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.

• 出版日期2012-8