Chop deletion reduces oxidative stress, improves β cell function, and promotes cell survival in multiple mouse models of diabetes

The progression from insulin resistance to type 2 diabetes is caused by the failure of pancreatic beta cells to produce sufficient levels of insulin to meet the metabolic demand. Recent studies indicate that nutrient fluctuations and insulin resistance increase proinsulin synthesis in beta cells beyond the capacity for folding of nascent polypeptides within the endoplasmic reticulum (ER) lumen, thereby disrupting ER homeostasis and triggering the unfolded protein response (UPR). Chronic ER stress promotes apoptosis, at least in part through the UPR-induced transcription factor C/EBP homologous protein (CHOP). We assessed the effect of Chop deletion in multiple mouse models of type 2 diabetes and found that…

• HH
  Howard Hughes Medical Institute
• UO
  University of Michigan

  Award: 48109
• NI
  National Institutes of Health

  Award: DK47119
• CO
  College of Pharmacy, University of Michigan
• NI
  National Institute of Diabetes and Digestive and Kidney Diseases