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

• Autor(a) principal: Giannocco, Gisele [UNIFESP]
• Data de Publicação: 2013
• Outros Autores: Oliveira, Kelen Carneiro [UNIFESP], Crajoinas, Renato O., Venturini, Gabriela, Salles, Thiago A., Fonseca-Alaniz, Miriam H., Maciel, Rui Monteiro de Barros [UNIFESP], Girardi, Adriana C. C.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1016/j.ejphar.2012.09.043; http://repositorio.unifesp.br/handle/11600/35873
• topic: Dipeptidyl peptidase IV; Glucose transporter type 4; Hypertension; Heart; Skeletal muscle; Glucagon-like peptide-1

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.