| Uncoupling protein 3 expression levels influence insulin sensitivity, fatty acid oxidation, and related signaling pathways. | |
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MedLine Citation:
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PMID: 21058020 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Controversy exists on whether uncoupling protein 3 (UCP3) positively or negatively influences insulin sensitivity in vivo, and the underlying signaling pathways have been scarcely studied. We studied how a progressive reduction in UCP3 expression (using UCP3 +/+, UCP3 +/-, and UCP3 -/- mice) modulates insulin sensitivity and related metabolic parameters. In order to further validate our observations, we also studied animals in which insulin resistance was induced by administration of a high-fat diet (HFD). In UCP3 +/- and UCP3 -/- mice, gastrocnemius muscle Akt/protein kinase B (Akt/PKB) (serine 473) and AMP-activated protein kinase (AMPK) (threonine 171) phosphorylation, and glucose transporter 4 (GLUT4) membrane levels were reduced compared to UCP3 +/+ mice. The HOMA-IR index (insulin resistance parameter) was increased both in the UCP3 +/- and UCP3 -/- mice. In these mice, insulin administration normalized Akt/PKB phosphorylation between genotypes while AMPK phosphorylation was further reduced, and sarcolemmal GLUT4 levels were induced but did not reach control levels. Furthermore, non-insulin-stimulated muscle fatty acid oxidation and the expression of several involved genes both in muscle and in liver were reduced. HFD administration induced insulin resistance in UCP3 +/+ mice and the aforementioned parameters resulted similar to those of chow-fed UCP3 +/- and UCP3 -/- mice. In conclusion, high-fat-diet-induced insulin resistance in wild-type mice mimics that of chow-fed UCP3 +/- and UCP3 -/- mice showing that progressive reduction of UCP3 levels results in insulin resistance. This is accompanied by decreased fatty acid oxidation and a less intense Akt/PKB and AMPK signaling. |
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Authors:
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Rosalba Senese; Vivien Valli; Maria Moreno; Assunta Lombardi; Rosa Anna Busiello; Federica Cioffi; Elena Silvestri; Fernando Goglia; Antonia Lanni; Pieter de Lange |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-07 |
Journal Detail:
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Title: Pflügers Archiv : European journal of physiology Volume: 461 ISSN: 1432-2013 ISO Abbreviation: Pflugers Arch. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-03 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0154720 Medline TA: Pflugers Arch Country: Germany |
Other Details:
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Languages: eng Pagination: 153-64 Citation Subset: IM |
Affiliation:
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Dipartimento di Scienze della Vita, Seconda Università degli Studi di Napoli, Via Vivaldi 43, Caserta, Italy. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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