TY - JOUR
T1 - When translation meets metabolism
T2 - Multiple links to diabetes
AU - Shi, Yuguang
AU - Taylor, Simeon I.
AU - Tan, Seng Lai
AU - Sonenberg, Nahum
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/2
Y1 - 2003/2
N2 - Type 2 diabetes is a polygenic disorder characterized by multiple biochemical defects including transcriptional, translational, and posttranslational abnormalities. Although major progress has been made in elucidation of factors at the transcriptional and posttranslational levels, defects at the translational level remain elusive. Mutation of a kinase that regulates translation initiation has been implicated in the etiology of a monogenic form of diabetes known as Wolcott-Rallison syndrome. Characterization of mice rendered deficient in eukaryotic initiation factors has provided model systems to study the involvement of translation in regulating insulin synthesis and secretion, hepatic function, peripheral insulin resistance, and diabetic complications. Recent progress in the understanding of endoplasmic reticulum overload by unfolded proteins has begun to uncover mechanisms leading to pancreatic β-cell exhaustion. Future advances in this area may lead to identification of the missing links in the pathogenesis of β-cell failures due to conditions such as hyperinsulinemia, hyperglycemia, and long-term treatment with sulfonylureas, and thus may identify novel therapeutic targets for diabetes.
AB - Type 2 diabetes is a polygenic disorder characterized by multiple biochemical defects including transcriptional, translational, and posttranslational abnormalities. Although major progress has been made in elucidation of factors at the transcriptional and posttranslational levels, defects at the translational level remain elusive. Mutation of a kinase that regulates translation initiation has been implicated in the etiology of a monogenic form of diabetes known as Wolcott-Rallison syndrome. Characterization of mice rendered deficient in eukaryotic initiation factors has provided model systems to study the involvement of translation in regulating insulin synthesis and secretion, hepatic function, peripheral insulin resistance, and diabetic complications. Recent progress in the understanding of endoplasmic reticulum overload by unfolded proteins has begun to uncover mechanisms leading to pancreatic β-cell exhaustion. Future advances in this area may lead to identification of the missing links in the pathogenesis of β-cell failures due to conditions such as hyperinsulinemia, hyperglycemia, and long-term treatment with sulfonylureas, and thus may identify novel therapeutic targets for diabetes.
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U2 - 10.1210/er.2002-0018
DO - 10.1210/er.2002-0018
M3 - Review article
C2 - 12588811
AN - SCOPUS:0037326359
SN - 0163-769X
VL - 24
SP - 91
EP - 101
JO - Endocrine Reviews
JF - Endocrine Reviews
IS - 1
ER -