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PMID: 20609972 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Lipid-induced insulin resistance: unravelling the mechanism.

Lancet (London, England) ·Vol. 375 ·No. 9733 ·2010-06-26 ·Pages 2267-77

Samuel VT, Petersen KF, Shulman GI

Abstract

Insulin resistance has long been associated with obesity. More than 40 years ago, Randle and colleagues postulated that lipids impaired insulin-stimulated glucose use by muscles through inhibition of glycolysis at key points. However, work over the past two decades has shown that lipid-induced insulin resistance in skeletal muscle stems from defects in insulin-stimulated glucose transport activity. The steatotic liver is also resistant to insulin in terms of inhibition of hepatic glucose production and stimulation of glycogen synthesis. In muscle and liver, the intracellular accumulation of lipids-namely, diacylglycerol-triggers activation of novel protein kinases C with subsequent impairments in insulin signalling. This unifying hypothesis accounts for the mechanism of insulin resistance in obesity, type 2 diabetes, lipodystrophy, and ageing; and the insulin-sensitising effects of thiazolidinediones.

MeSH Terms
Animals Diabetes Mellitus, Type 2/metabolism Diglycerides Fatty Acids/metabolism Fatty Liver/metabolism Glucose/metabolism Humans Insulin/metabolism Insulin Resistance/physiology Lipids/physiology Muscle, Skeletal/metabolism Obesity/metabolism Protein Kinase C/metabolism
Chemicals
Diglycerides Fatty Acids Insulin Lipids Protein Kinase C Glucose
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Samuel Varman T
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06536-8012, USA.
Petersen Kitt Falk
Shulman Gerald I
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Article Info
Journal
Lancet (London, England)
Abbr.
Lancet
ISSN
1474-547X
DOI
10.1016/S0140-6736(10)60408-4
Published
2010-06-26
Pages
2267-77
Language
English
Region
England
NLM ID
2985213R
PMCID
PMC2995547
Subset
IM
Grants
NCRR NIH HHS · UL1 RR024139 · United States
NIDDK NIH HHS · U24 DK-59635 · United States
NIA NIH HHS · R56 AG023686 · United States
Howard Hughes Medical Institute · United States
NIDDK NIH HHS · P01 DK-068229 · United States
NIDDK NIH HHS · P01 DK068229 · United States
NIDDK NIH HHS · R01 DK040936 · United States
NCRR NIH HHS · UL1RR024139 · United States
NIA NIH HHS · R01 AG023686 · United States
NIDDK NIH HHS · P30 DK045735 · United States
NIA NIH HHS · R01 AG023686-06A2 · United States
NIA NIH HHS · R01 AG-23686, · United States
NIA NIH HHS · R01 AG023686-07 · United States
NCRR NIH HHS · K23 RR017404 · United States
NIDDK NIH HHS · R01 DK049230 · United States
NIDDK NIH HHS · R01 DK-49230, · United States
NIDDK NIH HHS · R01 DK-40936 · United States
NCRR NIH HHS · K23 RR17404 · United States
NCRR NIH HHS · UL1 RR-024139 · United States
NIDDK NIH HHS · U24 DK059635 · United States
NIA NIH HHS · R56 AG023686-06A1 · United States
NIDDK NIH HHS · P30DK-45735, · United States
External Links
PubMed source DOI: 10.1016/S0140-6736(10)60408-4 PMC Full Text View journal details
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