PERK in beta cell biology and insulin biogenesis

被引：62

作者：

Cavener, Douglas R. ^{[1
,2
]}

Gupta, Sounak ^{[1
,2
]}

McGrath, Barbara C. ^{[1
,2
]}

机构：

[1] Penn State Univ, Dept Biol, Ctr Cellular Dynam, University Pk, PA 16802 USA

[2] Penn State Univ, Penn State Inst Diabet & Obes, University Pk, PA 16802 USA

来源：

TRENDS IN ENDOCRINOLOGY AND METABOLISM | 2010年 / 21卷 / 12期

关键词：

ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; WOLCOTT-RALLISON-SYNDROME; TRANSLATIONAL CONTROL; DIABETES-MELLITUS; GLUCOSE-HOMEOSTASIS; MAMMALIAN DEVELOPMENT; GENE-EXPRESSION; MESSENGER-RNA; PATHWAY;

D O I：

10.1016/j.tem.2010.08.005

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

PERK (EIF2AK3) was originally discovered as a major component of the unfolded protein response (UPR). PERK deficiency results in permanent neonatal diabetes, which was initially thought to be caused by a failure to regulate ER stress in insulin-secreting beta cells, culminating in beta cell death. However, subsequent studies found that low beta cell mass was a result of reduced cell proliferation, rather than increased apoptosis. Genetic and cellular studies of Perk-deficient beta cells showed that PERK was crucially required for ER functions including proinsulin trafficking and quality control, unrelated to the ER stress pathway. Under normal physiological conditions, changes in ER calcium levels, mediated by glucose and other insulin secretagogues, regulate PERK activity for the purpose of controlling insulin biogenesis.

引用

收藏

页码：714 / 721

页数：8

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