UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

1-26-2010

Document Type

Article

Medical Subject Headings

Endoplasmic Reticulum; Unfolded Protein Response; Insulin-Secreting Cells; Diabetes Mellitus; Wolfram Syndrome

Disciplines

Genetics and Genomics

Abstract

In pancreatic beta-cells, the endoplasmic reticulum (ER) is the crucial site for insulin biosynthesis, as this is where the protein-folding machinery for secretory proteins is localized. Perturbations to ER function of the beta-cell, such as a high demand for insulin secretion, can lead to an imbalance in protein homeostasis and lead to ER stress. This stress can be mitigated by an adaptive, cellular response, the unfolded protein response (UPR). UPR activation is vital to the survival of beta-cells, as these cells represent one of the most susceptible tissues for ER stress, due to their highly secretory function. However, in some cases, this response is not sufficient to relieve stress, leading to apoptosis and contributing to the pathogenesis of diabetes. Recent evidence shows that ER stress plays a significant role in both type 1 and type 2 diabetes. In this review, we outline the mechanisms of ER stress-mediated beta-cell death and focus on the role of ER stress in various forms of diabetes, particularly a genetic form of diabetes called Wolfram syndrome.

Rights and Permissions

Citation: Islets. 2010 Jan-Feb;2(1):1-9. Link to article on publisher's site

Related Resources

Link to Article in PubMed

 
 

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