**Author details**

Jixin Zhong1,2

tory cytokines, leading to excessive production of nitric oxygenand β cell destruction in an ER stress-dependent pathway. ER stress also regulates the functionality of immune cells with implications in autoimmune progression. The inadequate insulin secretion in patients with type 1 diabetes renders the residual β cells for compensated insulin secre‐ tion to maintain blood glucose homeostasis. This increase in insulin biosynthesis could overwhelm the folding capacity of ER, and exacerbate β cell dysfunction by inducing ER

Although ER stress is a critical factor involved in the pathogenesis of type 1 diabetes, it should be kept in mind that the mechanisms underlying autoimmune-mediated β cell de‐ struction in type 1 diabetes are complex, and ER stress is unlikely the exclusive mechanism implicated in disease process. Despite recent significant progress in this area, there are still many questions yet to be addressed. Are there additional factors inducing ER stress in β cells during type 1 diabetes development? Can ER stress be served as a biomarker for β cell destruction and autoimmune progression in the clinic setting? Does blockade of ER stress in immune cells attenuate autoimmune progression and protect β cells? Future studies aimed to dissect these questions would provide a deep insight for type 1 diabetes pathogenesis and would have great potential for developing novel therapeutic strategies against this devastat‐

This work is supported by a grant from the National Natural Science Foundation of China

AP1, activator protein 1; Ask1, apoptosis signal-regulating kinase 1; ATF6, Activating Tran‐ scription Factor 6; C/EBP, CCAAT/enhancer binding protein; CHOP, C/EBP homologous protein; CREBH, Cyclic-AMP-responsive-element-binding protein H; eIF2α, eukaryotic ini‐ tiation factor 2α; ER, Endoplasmic Reticulum; ER stress, Endoplasmic Reticulum stress; iNOS, inducible nitric oxide synthase; IRE1, inositol-requiring enzyme 1; IRS-1, insulin re‐ ceptor substrate-1; JIK, c-Jun N-terminal inhibitory kinase; JNK, c-Jun N-terminal kinases; NRF2, nuclear factor-erythroid-derived 2-related factor 2; PERK, pancreatic endoplasmic re‐ ticulum kinase; RER, rough endoplasmic reticulum; ROS, reactive oxygen species; SER, smooth endoplasmic reticulum; TLR, Toll-like receptor; TRAF2, TNF receptor-associated factor 2; TRIF, Toll-IL-1R-containing adaptor inducing IFN-β; UPR, unfolded protein re‐

(81101553/H1604) to JZ. The author declares no competing financial interest.

stress in β cells.

210 Type 1 Diabetes

ing disorder.

**Acknowledgements**

**Abbreviations**

sponse; XBP-1, X box protein-1.

Address all correspondence to: zhongjixin620@163.com

1 Department of Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China

2 Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio, USA
