Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation.

Insulin-secreting pancreatic beta-cells are extremely dependent on their endoplasmic reticulum ( ER) to cope with the oscillatory requirement of secreted insulin to maintain normoglycemia. Insulin translation and folding rely greatly on the unfolded protein response ( UPR), an array of three main signaling pathways designed to maintain ER homeostasis and limit ER stress. However, prolonged or excessive UPR activation triggers alternative molecular pathways that can lead to beta-cell dysfunction and apoptosis. An increasing number of studies suggest a role of these pro-apoptotic UPR pathways in the downfall of beta-cells observed in diabetic patients. Particularly, the past few years highlighted a cross talk between the UPR and inflammation in the context of both type 1 ( T1D) and type 2 diabetes ( T2D). In this article, we describe the recent advances in research regarding the interplay between ER stress, the UPR, and inflammation in the context of beta-cell apoptosis leading to diabetes.