| IGF-I stimulates reactive oxygen species (ROS) production and inhibits insulin-dependent glucose uptake via ROS in 3T3-L1 adipocytes. | |
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MedLine Citation:
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PMID: 20185348 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: IGF-I is known to enhance insulin sensitivity in whole body mainly via the IGF-I receptors in muscles. However, the effect of IGF-I on the regulation of insulin sensitivity in the adipose tissue is yet unclear. Insulin sensitivity was found to be higher in the IGF-I receptor-deficient adipocytes than that in wild-type adipocytes, suggesting that IGF-I signaling induces insulin resistance in adipocytes. However, the underlying mechanism has not yet been elucidated. In addition, the effect of superphysiological levels of IGF-I, as is observed in patients with acromegaly, on insulin sensitivity remains unclear. DESIGN: To clarify the role of IGF-I on insulin sensitivity in adipocytes, we determined insulin-induced glucose uptake and IRS-1 status in 3T3-L1 adipocytes treated with IGF-I. Since reactive oxygen species (ROS) are causally related to insulin resistance, we investigated the effect of IGF-I on ROS production to elucidate the molecular mechanism underlying insulin resistance. RESULTS: Preincubation of the adipocytes with IGF-I attenuated insulin-dependent glucose uptake. Interestingly, we found that IGF-I significantly stimulated ROS production. Furthermore, preincubation of adipocytes with an antioxidant, N-acetyl-cysteine (NAC) restored the IGF-I-induced attenuation of insulin-dependent glucose uptake; this indicates that IGF-I induces insulin resistance via ROS. Serine phosphorylation of IRS-1 was strongly induced and the insulin-dependent tyrosine phosphorylation of IRS-1 was suppressed by preincubating the adipocytes with IGF-I. Further, NAC restored these changes induced by IGF-I on both serine and tyrosine phosphorylation of IRS-1. CONCLUSIONS: These data indicate that IGF-I inhibited insulin activity in the 3T3-L1 adipocytes via ROS production, which affects IRS-1 phosphorylation status. |
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Authors:
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Hidenori Fukuoka; Keiji Iida; Hitoshi Nishizawa; Mari Imanaka; Ryoko Takeno; Genzo Iguchi; Michiko Takahashi; Yasuhiko Okimura; Hidesuke Kaji; Kazuo Chihara; Yutaka Takahashi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-24 |
Journal Detail:
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Title: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society Volume: 20 ISSN: 1532-2238 ISO Abbreviation: Growth Horm. IGF Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-24 Completed Date: 2010-09-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9814320 Medline TA: Growth Horm IGF Res Country: Scotland |
Other Details:
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Languages: eng Pagination: 212-9 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adipocytes / drug effects*, metabolism Animals Glucose / pharmacokinetics* Insulin / pharmacology* Insulin Receptor Substrate Proteins / metabolism Insulin Resistance / physiology Insulin-Like Growth Factor I / pharmacology* Mice NADPH Oxidase / metabolism Oxidative Stress / physiology Phosphorylation / drug effects Reactive Oxygen Species / metabolism*, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, mouse; 0/Reactive Oxygen Species; 11061-68-0/Insulin; 50-99-7/Glucose; 67763-96-6/Insulin-Like Growth Factor I; EC 1.6.3.1/NADPH Oxidase |
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