TY - JOUR
T1 - Monogenic and syndromic diabetes due to endoplasmic reticulum stress
AU - Stone, Stephen I.
AU - Abreu, Damien
AU - McGill, Janet B.
AU - Urano, Fumihiko
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - The endoplasmic reticulum (ER) lies at the crossroads of protein folding, calcium storage, lipid metabolism, and the regulation of autophagy and apoptosis. Accordingly, dysregulation of ER homeostasis leads to β-cell dysfunction in type 1 and type 2 diabetes that ultimately culminates in cell death. The ER is therefore an emerging target for understanding the mechanisms of diabetes mellitus that captures the complex etiologies of this multifactorial class of metabolic disorders. Our strategy for developing ER-targeted diagnostics and therapeutics is to focus on monogenic forms of diabetes related to ER dysregulation in an effort to understand the exact contribution of ER stress to β-cell death. In this manner, we can develop personalized genetic medicine for ERstress-related diabetic disorders, such as Wolfram syndrome. In this article, we describe the phenotypes and molecular pathogenesis of ERstress-related monogenic forms of diabetes.
AB - The endoplasmic reticulum (ER) lies at the crossroads of protein folding, calcium storage, lipid metabolism, and the regulation of autophagy and apoptosis. Accordingly, dysregulation of ER homeostasis leads to β-cell dysfunction in type 1 and type 2 diabetes that ultimately culminates in cell death. The ER is therefore an emerging target for understanding the mechanisms of diabetes mellitus that captures the complex etiologies of this multifactorial class of metabolic disorders. Our strategy for developing ER-targeted diagnostics and therapeutics is to focus on monogenic forms of diabetes related to ER dysregulation in an effort to understand the exact contribution of ER stress to β-cell death. In this manner, we can develop personalized genetic medicine for ERstress-related diabetic disorders, such as Wolfram syndrome. In this article, we describe the phenotypes and molecular pathogenesis of ERstress-related monogenic forms of diabetes.
KW - ER stress
KW - Endoplasmic reticulum
KW - Genetic medicine
KW - Genetic testing
KW - Personalized medicine
KW - Wolfram syndrome
UR - http://www.scopus.com/inward/record.url?scp=85086014729&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2020.107618
DO - 10.1016/j.jdiacomp.2020.107618
M3 - Article
C2 - 32518033
AN - SCOPUS:85086014729
VL - 35
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
SN - 1056-8727
IS - 1
M1 - 107618
ER -