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Cell. 2012 Mar 2;148(5):852-71. doi: 10.1016/j.cell.2012.02.017.

Mechanisms for insulin resistance: common threads and missing links.

Author information

  • 1Department of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA. varman.samuel@yale.edu

Abstract

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.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22385956
[PubMed - indexed for MEDLINE]
PMCID:
PMC3294420
Free PMC Article
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