Mechanisms for Insulin Resistance: Common Threads and Missing Links

被引：1605

作者：

Samuel, Varman T. ^{[1
,4
]}

Shulman, Gerald I. ^{[1
,2
,3
]}

机构：

[1] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA

[3] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

[4] Vet Affairs Med Ctr, West Haven, CT 06516 USA

来源：

CELL | 2012年 / 148卷 / 05期

关键词：

PROTEIN-KINASE-C; FATTY LIVER-DISEASE; ADIPOSE TRIGLYCERIDE LIPASE; TUMOR-NECROSIS-FACTOR; ENDOPLASMIC-RETICULUM STRESS; DIET-INDUCED OBESITY; NF-KAPPA-B; DEPENDENT DIABETES-MELLITUS; INDUCED HEPATIC STEATOSIS; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY;

D O I：

10.1016/j.cell.2012.02.017

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Insulin resistance is a complex metabolic disorder that defies explanation by a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway, and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, these cellular changes may converge to promote the accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, a common final pathway leading to impaired insulin signaling and insulin resistance.

引用

页码：852 / 871

页数：20

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