| Irbesartan enhances GLUT4 translocation and glucose transport in skeletal muscle cells. | |
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MedLine Citation:
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PMID: 20826135 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Irbesartan, an angiotensin II type 1 receptor blocker has been reported to alleviate metabolic disorder in animal studies and human clinical trials. Although this effect may be related to the ability of irbesartan to serve as a partial agonist for the peroxisome proliferator-activated receptor (PPAR)-γ, the target tissues on which irbesartan acts remain poorly defined. As muscle glucose transport plays a major role in maintaining systemic glucose homeostasis, we investigated the effect of irbesartan on glucose uptake in skeletal muscle cells. In C2C12 myotubes, 24-h treatment with irbesartan significantly promoted both basal and insulin-stimulated glucose transport. In L6-GLUT4myc myoblasts, irbesartan caused a significant increase in glucose transport and GLUT4 translocation to the cell surface in a concentration-dependent manner. Valsartan, another angiotensin II type 1 receptor blocker had no effect on either glucose uptake or GLUT4 translocation, implying that these actions on glucose transport are independent of angiotensin II receptor blockade. Moreover, irbesartan exerted these effects in an additive manner with insulin, but not with acute treatment for 3 h, suggesting that they may require the synthesis of new proteins. Finally, in insulin-resistant Zucker fatty rat, irbesartan (50 mg/kg/day for 3 weeks) significantly ameliorated insulin resistance without increasing weight gain. We conclude that irbesartan has a direct action, which can be additive to insulin, of promoting glucose transport in skeletal muscle. This may be beneficial for ameliorating obesity-related glucose homeostasis derangement. |
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Authors:
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Tatsuo Kobayashi; Yuko Akiyama; Nobuteru Akiyama; Hideaki Katoh; Sachiko Yamamoto; Kenzo Funatsuki; Toru Yanagimoto; Mitsuru Notoya; Kenji Asakura; Toshihiro Shinosaki; Kohji Hanasaki |
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Publication Detail:
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Type: Journal Article Date: 2010-09-06 |
Journal Detail:
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Title: European journal of pharmacology Volume: 649 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-01 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 23-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Discovery Research Laboratories, Shionogi & Co., Ltd., Osaka 561-0825, Japan. tatsuo.kobayashi@shionogi.co.jp |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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