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.
|Autori:||Jain D; Jain R; Eberhard D; Eglinger J; Bugliani M; Piemonti L; Marchetti P; Lammert E|
|Titolo:||Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with implications for human type 2 diabetes|
|Anno del prodotto:||2012|
|Digital Object Identifier (DOI):||10.1093/jmcb/mjs025|
|Appare nelle tipologie:||1.1 Articolo in rivista|