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

Autor(es)

Giannocco, Gisele ^{[1, 2]} ; Oliveira, Kelen C. ^{[1, 2]} ; Crajoinas, Renato O. ^[3] ; Venturini, Gabriela ^[3] ; Salles, Thiago A. ^[3] ; Fonseca-Alaniz, Miriam H. ^[3] ; Maciel, Rui M. B. ^[1] ; Girardi, Adriana C. C. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Med, Sao Paulo - Brazil

^[2] Fac Med ABC, Dept Morphol & Physiol, Sao Paulo - Brazil

^[3] Univ Sao Paulo Med Sch, Inst Heart, Lab Genet & Mol Cardiol, BR-05403900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 698, n. 1-3, p. 74-86, JAN 5 2013.
• Citações Web of Science: 30

Resumo

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. (AU)

• Processo FAPESP: 07/52945-8 - Importância do peptídeo semelhante ao glucagon 1 (GLP-1) na manutenção do volume extracelular: abordagem funcional, farmacológica e molecular
• Beneficiário: Adriana Castello Costa Girardi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores