| Inhibition of PTP1B by trodusquemine (MSI-1436) causes fat-specific weight loss in diet-induced obese mice. | |
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MedLine Citation:
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PMID: 20075852 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Trodusquemine (MSI-1436) causes rapid and reversible weight loss in genetic models of obesity. To better predict the potential effects of trodusquemine in the clinic, we investigated the effects of trodusquemine treatment in a murine model of diet-induced obesity (DIO). Trodusquemine suppressed appetite, reduced body weight (BW) in a fat-specific manner, and improved plasma insulin and leptin levels in mice. Screening assays revealed that trodusquemine selectively inhibited protein-tyrosine phosphatase 1B (PTP1B), a key enzyme regulating insulin and leptin signaling. Trodusquemine significantly enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) beta and STAT3, direct targets of PTP1B, in HepG2 cells in vitro and/or hypothalamic tissue in vivo. These data establish trodusquemine as an effective central and peripheral PTP1B inhibitor with the potential to elicit noncachectic fat-specific weight loss and improve insulin and leptin levels. |
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Authors:
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Kristen A Lantz; Susan G Emeigh Hart; Sonia L Planey; Mitchell F Roitman; Inez A Ruiz-White; Henry R Wolfe; Michael P McLane |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-14 |
Journal Detail:
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Title: Obesity (Silver Spring, Md.) Volume: 18 ISSN: 1930-7381 ISO Abbreviation: Obesity (Silver Spring) Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101264860 Medline TA: Obesity (Silver Spring) Country: United States |
Other Details:
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Languages: eng Pagination: 1516-23 Citation Subset: IM |
Affiliation:
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Department of Preclinical Research, Genaera Corporation, Plymouth Meeting, Pennsylvania, USA. |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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1R43DK066953-01/DK/NIDDK NIH HHS |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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