Dipeptidyl peptidase IV inhibition upregulates GLUT4 translocation and expression in heart and skeletal muscle of spontaneously hypertensive rats

Dipeptidyl peptidase IV inhibition upregulates GLUT4 translocation and expression in heart and skeletal muscle of spontaneously hypertensive rats

Author Giannocco, Gisele Autor UNIFESP Google Scholar
Oliveira, Kelen Carneiro Autor UNIFESP Google Scholar
Crajoinas, Renato O. Google Scholar
Venturini, Gabriela Google Scholar
Salles, Thiago A. Google Scholar
Fonseca-Alaniz, Miriam H. Google Scholar
Maciel, Rui Monteiro de Barros Autor UNIFESP Google Scholar
Girardi, Adriana C. C. Google Scholar
Institution Fac Med ABC
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract 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 (40 mg/kg twice daily) decreased plasma DPPIV activity in both young (Y, 5-week-old) and adult (A, 20-week-old) SHRs to similar extents ( similar to 85%). However, DPPIV inhibition only lowered blood pressure in Y-SHRs (119 +/- 3 vs. 136 +/- 4 mmHg). 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. (C) 2012 Elsevier B.V. All rights reserved.
Keywords Dipeptidyl peptidase IV
Glucose transporter type 4
Hypertension
Heart
Skeletal muscle
Glucagon-like peptide-1
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number FAPESP: 2007/52945-8
CNPq: 480775/2007-9
Date 2013-01-05
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 698, n. 1-3, p. 74-86, 2013.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 74-86
Origin http://dx.doi.org/10.1016/j.ejphar.2012.09.043
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000314616200009
URI http://repositorio.unifesp.br/handle/11600/35873

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