Endoplasmic reticulum stress is involved in the connection between inflammation and autophagy in type 2 diabetes

Type 2 diabetes is a chronic inflammatory disease. A number of studies have clearly demonstrated that cytokines such as interleukin 1 beta (IL1 beta) contribute to pancreatic inflammation, leading to impaired glucose homeostasis and diabetic disease. There are findings which suggest that islet beta-cells can secrete cytokines and cause inflammatory responses. In this process, thioredoxin-interacting protein (TXNIP) is induced by endoplasmic reticulum (ER) stress, which further demonstrates a potential role for ER stress in innate immunity via activation of the NOD-like receptor (NLRP) 3/caspasel inflammasome and in diabetes pathogenesis via the release of cytokines. Recent developments have also revealed a crucial role for the autophagy pathway during ER stress and inflammation. Autophagy is an intracellular catabolic system that not only plays a crucial role in maintaining the normal islet architecture and intracellular insulin content but also represents a form of programmed cell death. In this review, we focus on the roles of autophagy, inflammation, and ER stress in type 2 diabetes but, above all, on the connections among these factors. (C) 2014 Elsevier Inc. All rights reserved.