| Improvement of insulin resistance by removal of systemic hydrogen peroxide by PEGylated catalase in obese mice. | |
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MedLine Citation:
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PMID: 21033698 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Insulin resistance, a condition in which insulin action is impaired, is one of the characteristic features of type 2 diabetes. Excessive amounts of reactive oxygen species (ROS) interfere with the insulin signaling pathway, which leads to the progression of insulin resistance. To examine whether removal of systemic hydrogen peroxide is effective in improving insulin resistance, polyethylene glycol-conjugated catalase (PEG-catalase), a derivative with a long circulation half-life, was repeatedly injected into leptin-deficient ob/ob or high fat diet-induced obese mice for 16 or 10 consecutive weeks, respectively. Although ob/ob mice gradually gained weight with time irrespective of the treatment, repeated intraperitoneal injections of PEG-catalase significantly reduced glucose levels in the fed state. Glucose and insulin tolerance tests also showed PEG-catalase significantly improved glucose tolerance and insulin sensitivity in ob/ob mice, respectively. Similar but less marked results were obtained in the diet-induced obese mice. Treatment of 3T3-L1 adipocytes with glucose oxidase (GO) increased lipid hydroperoxide formation and reduced insulin-stimulated Akt phosphorylation. Addition of catalase or PEG-catalase significantly inhibited the GO-induced changes in adipocytes. These findings indicate that systemic removal of hydrogen peroxide by PEG-catalase activates the insulin signaling pathway and improves insulin resistance in obese mice. |
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Authors:
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Mai Ikemura; Makiya Nishikawa; Kenji Hyoudou; Yuki Kobayashi; Fumiyoshi Yamashita; Mitsuru Hashida |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-15 |
Journal Detail:
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Title: Molecular pharmaceutics Volume: 7 ISSN: 1543-8392 ISO Abbreviation: Mol. Pharm. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: United States |
Other Details:
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Languages: eng Pagination: 2069-76 Citation Subset: IM |
Affiliation:
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Department of Drug Delivery Research and Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, and Institute for Integrated Cell-Material Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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