A reevaluation of the role of the unfolded protein response in islet dysfunction: Maladaptation or a failure to adapt?

Herbert, T and Laybutt, R 2016, 'A reevaluation of the role of the unfolded protein response in islet dysfunction: Maladaptation or a failure to adapt?', Diabetes, vol. 65, no. 6, pp. 1472-1480.


Document type: Journal Article
Collection: Journal Articles

Title A reevaluation of the role of the unfolded protein response in islet dysfunction: Maladaptation or a failure to adapt?
Author(s) Herbert, T
Laybutt, R
Year 2016
Journal name Diabetes
Volume number 65
Issue number 6
Start page 1472
End page 1480
Total pages 9
Publisher American Diabetes Association Inc.
Abstract Endoplasmic reticulum (ER) stress caused by perturbations in ER homeostasis activates an adaptive response termed the unfolded protein response (UPR) whose function is to resolve ER stress. If unsuccessful, the UPR initiates a proapoptotic program to eliminate the malfunctioning cells from the organism. It is the activation of this proapoptotic UPR in pancreatic β-cells that has been implicated in the onset of type 2 diabetes and thus, in this context, is considered a maladaptive response. However, there is growing evidence that β-cell death in type 2 diabetes may not be caused by a maladaptive UPR but by the inhibition of the adaptive UPR. In this review, we discuss the evidence for a role of the UPR in β-cell dysfunction and death in the development of type 2 diabetes and ask the following question: Is β-cell dysfunction the result of a maladaptive UPR or a failure of the UPR to adequately adapt? The answer to this question is critically important in defining potential therapeutic strategies for the treatment and prevention of type 2 diabetes. In addition, we discuss the potential role of the adaptive UPR in staving off type 2 diabetes by enhancing β-cell mass and function in response to insulin resistance.
Subject Endocrinology
Keyword(s) endoplasmic-reticulum stress
pancreatic beta-cells
high-fat-diet
thioredoxin-interacting protein
induced insulin-resistance
initiation-factor 2-alpha
er stress
oxidative stress
glucose-homeostasis
diabetes-mellitus
DOI - identifier 10.2337/db15-1633
Copyright notice © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
ISSN 0012-1797
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