| Toll-like receptor 2 deficiency improves insulin sensitivity and hepatic insulin signalling in the mouse. | |
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MedLine Citation:
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PMID: 20967535 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: Substantial evidence suggests a link between elevated inflammation and development of insulin resistance. Toll-like receptor 2 (TLR2) recognises a large number of lipid-containing molecules and transduces inflammatory signalling in a variety of cell types, including insulin-responsive cells. Considering the contribution of the fatty acid composition in TLR2-depedent signalling, we hypothesised that the inflammatory signals transduced by TLR2 contribute to insulin resistance. METHODS: Mice deficient in TLR2 were used to investigate the in vivo roles of TLR2 in initiating and maintaining inflammation-associated insulin resistance and energy homeostasis. RESULTS: We first recapitulated the observation with elevated expression of TLR2 and inflammatory cytokines in white adipose tissue and liver of ob/ob mice. Aged or high-fat-fed TLR2-deficient mice were protected from obesity and adipocyte hypertrophy compared with wild-type mice. Moreover, mice lacking TLR2 exhibited improved glucose tolerance and insulin sensitivity regardless of feeding them regular chow or a high-fat diet. This is accompanied by reductions in expression of inflammatory cytokines and activation of extracellular signal-regulated kinase (ERK) in a liver-specific manner. The attenuated hepatic inflammatory cytokine expression and related signalling are correlated with increased insulin action specifically in the liver in TLR2-deficient mice, reflected by increased insulin-stimulated protein kinase B (Akt) phosphorylation and IRS1 tyrosine phosphorylation and increased insulin-suppressed hepatocyte glucose production. CONCLUSIONS/INTERPRETATION: The absence of TLR2 attenuates local inflammatory cytokine expression and related signalling and increases insulin action specifically in the liver. Thus, our work has identified TLR2 as a key mediator of hepatic inflammation-related signalling and insulin resistance. |
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Authors:
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L-H Kuo; P-J Tsai; M-J Jiang; Y-L Chuang; L Yu; K-T A Lai; Y-S Tsai |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-22 |
Journal Detail:
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Title: Diabetologia Volume: 54 ISSN: 1432-0428 ISO Abbreviation: Diabetologia Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 168-79 Citation Subset: IM |
Affiliation:
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Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, Republic of China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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