Increased insulin sensitivity and diminished pancreatic beta-cell function in DNA repair deficient Ercc1 mice

BackgroundType 2 diabetes (T2DM) is an age-associated disease characterized by hyperglycemia due to insulin resistance and decreased beta-cell function. DNA damage accumulation has been associated with T2DM, but whether plays a role in the pathogenesis of unclear. Here, we used mice deficient for excision-repair gene Ercc1 study impact persistent endogenous on energy metabolism, glucose homeostasis function.MethodsERCC1-XPF endonuclease required multiple repair pathways reduced expression ERCC1-XPF causes accelerated unrepaired aging humans mice. In this study, function sensitivity were studied Ercc1d/− mice, which model human progeroid syndrome.ResultsErcc1d/− displayed suppression somatotropic axis altered metabolism. Insulin was increased, whereas, plasma levels Fasting induced hypoglycemia result increased disposal. exhibit significantly area, even compared control similar weight. Glucose-stimulated secretion vivo Islets isolated from showed markers, glucose-stimulated susceptibility apoptosis.ConclusionSpontaneous triggers adaptive response resulting improved sensitivity. Loss repair, however, does negatively impacts survival