| Dipeptidyl peptidase IV inhibition upregulates GLUT4 translocation and expression in heart and skeletal muscle of spontaneously hypertensive rats. | |
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MedLine Citation:
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PMID: 23051671 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The purpose of the current study was to test the hypothesis that the dipeptidyl peptidase IV (DPPIV) inhibitor sitagliptin, which exerts anti-hyperglycemic and anti-hypertensive effects, upregulates GLUT4 translocation, protein levels, and/or mRNA expression in heart and skeletal muscle of spontaneously hypertensive rats (SHRs). Ten days of treatment with sitagliptin (40mg/kg twice daily) decreased plasma DPPIV activity in both young (Y, 5-week-old) and adult (A, 20-week-old) SHRs to similar extents (∼85%). However, DPPIV inhibition only lowered blood pressure in Y-SHRs (119±3vs. 136±4mmHg). GLUT4 translocation, total protein levels and mRNA expression were decreased in the heart, soleus and gastrocnemius muscle of SHRs compared to age-matched Wistar Kyoto (WKY) normotensive rats. These differences were much more pronounced between A-SHRs and A-WKY rats than between Y-SHRs and Y-WKY rats. In Y-SHRs, sitagliptin normalized GLUT4 expression in the heart, soleus and gastrocnemius. In A-SHRs, sitagliptin increased GLUT4 expression to levels that were even higher than those of A-WKY rats. Sitagliptin enhanced the circulating levels of the DPPIV substrate glucagon-like peptide-1 (GLP-1) in SHRs. In addition, stimulation of the GLP-1 receptor in cardiomyocytes isolated from SHRs increased the protein level of GLUT4 by 154±13%. Collectively, these results indicate that DPPIV inhibition upregulates GLUT4 in heart and skeletal muscle of SHRs. The underlying mechanism of sitagliptin-induced upregulation of GLUT4 in SHRs may be, at least partially, attributed to GLP-1. |
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Authors:
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Gisele Giannocco; Kelen C Oliveira; Renato O Crajoinas; Gabriela Venturini; Thiago A Salles; Miriam H Fonseca-Alaniz; Rui M B Maciel; Adriana C C Girardi |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-7 |
Journal Detail:
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Title: European journal of pharmacology Volume: - ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier B.V. |
Affiliation:
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Department of Morphology and Physiology, Faculdade de Medicina do ABC, Santo André, São Paulo, SP, Brazil; Department of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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