Volume 24, No 9, Sep 2014

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 24 Issue 9, September 2014: 1137-1140

LETTERS TO THE EDITOR

The IRE1α-XBP1 pathway regulates metabolic stress-induced compensatory proliferation of pancreatic β-cells

Tongfu Xu^1,*, Liu Yang^2,*, Cheng Yan², Xiaoxia Wang², Ping Huang², Feng Zhao², Liyun Zhao^2,3, Mingliang Zhang⁴, Weiping Jia⁴, Xiangdong Wang¹ and Yong Liu^2,5,6

¹Department of Cell Biology, Shandong University School of Medicine, 44 Wenhua Road West, Jinan, Shandong 250012, China
²Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
³China Novartis Institutes for BioMedical Research, Shanghai 201203, China
⁴Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
⁵School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China
⁶University of the Chinese Academy of Sciences, Shanghai 201203, China Correspondence: Yong Liu, E-mail: liuy@sibs.ac.cn; Xiangdong Wang,(xdongw@sdu.edu.cn)

In eukaryotes, increased protein folding demand at the endoplasmic reticulum (ER) activates the unfolded protein response (UPR)1, which plays a pivotal role in control of cellular functions and survival under ER stress2. Chronic ER stress is thought to contribute to the pathogenic progression of diabetes3,4. Inositol-requiring enzyme 1 (IRE1), an ER-resident transmembrane Ser/Thr protein kinase and endoribonuclease, is the most conserved ER stress sensor that mediates a key branch of the UPR1. In mammals, activation of IRE1α results in non-conventional splicing of the mRNA encoding the transcription factor X-box binding protein 1 (XBP1), generating a spliced active form of XBP1 (XBP1s) to initiate a major UPR program1. The IRE1-XBP1 pathway has been implicated in the homeostatic regulation of pancreatic islet β-cells. Whereas glucose-stimulated IRE1α activation is coupled to insulin production5,6,7, IRE1α also degrades insulin mRNAs under severe ER stress conditions8. Interestingly, genetic deletion of XBP1 in β-cells of mice was reported to result in a feedback hyperactivation of IRE1α, causing defective proinsulin processing and insulin secretion9. However, the precise role in vivo of IRE1α in integrating metabolic ER stress signals to regulate β-cell functions remains largely elusive.

10.1038/cr.2014.55

FULL TEXT | PDF

Browse 2249