| Both type I and II IFN Induces Insulin Resistance by Inducing Different Isoform of SOCS Expression in 3T3-L1 Adipocytes. | |
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MedLine Citation:
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PMID: 21386060 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Although elevation of the blood glucose level is a causal adverse effect of treatment with interferon (IFN), the precise underlying molecular mechanism is largely unknown. We examined the effects of type I and type II IFN (IFNβ and IFNγ) on insulin-induced metabolic signaling leading to glucose uptake in 3T3-L1 adipocytes. IFNβ suppressed insulin-induced tyrosine phosphorylation of IRS1 without affecting its expression, whereas IFNγ reduced both the protein level and tyrosine phosphorylation. Although both IFNs stimulated phosphorylation of Stat1 (at Tyr(701)) and Stat3 (at Tyr(705)) after treatment for 30 min, subsequent properties of induction of the SOCS isoform were different. IFNβ preferentially induced SOCS1 rather than SOCS3, while IFNγ strongly induced SOCS3 expression alone. In addition, either adenovirus-mediated overexpression of SOCS1 or SOCS3 inhibited insulin-induced tyrosine phosphorylation of IRS1, whereas the reduction of IRS1 protein was observed only in SOCS3-expressed cells. Notably, IFNβ-induced SOCS1 expression and suppression of insulin-induced tyrosine phosphorylation of IRS1 were attenuated by siRNA-mediated knockdown of Stat1. In contrast, adenovirus-mediated expression of a dominant-negative Stat3 (F-Stat3) attenuated IFNγ-induced SOCS3 expression, reduction of IRS1 protein, and suppression of insulin-induced glucose uptake, but did not have any effect on the IFNβ-mediated SOCS1 expression and inhibition of insulin-induced glucose uptake. Interestingly, pretreatment of IFNγ with IL6 synergistically suppressed insulin signaling, even when IL6 alone had no significant effect. These results indicate that type I and type II IFN cause insulin resistance by inducing distinct SOCS isoforms, and IL6 synergistically augments IFNγ-induced insulin resistance by potentiating Stat3-mediated SOCS3 induction in 3T3L1 adipocytes. |
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Authors:
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Tsutomu Wada; Masashi Hoshino; Yukari Kimura; Minoru Ojima; Tetsuro Nakano; Daisuke Koya; Hiroshi Tsuneki; Toshiyasu Sasaoka |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-8 |
Journal Detail:
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Title: American journal of physiology. Endocrinology and metabolism Volume: - ISSN: 1522-1555 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901226 Medline TA: Am J Physiol Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Toyama. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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