Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/51221
Title: Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: Role of GLP-1 isoforms in Glut4 receptor trafficking
Authors: Ramírez, E.
Picatoste, B.
González-Bris, A.
Oteo, M.
Cruz, F.
Caro-Vadillo, A. 
Egido, J.
Tuñón, J.
Morcillo, M. A.
Lorenzo, Ó
Issue Date: 2018
Project: CCG10-UAM/BIO-5289
PIE13/00051
PI14/00386
SAF2009-08367
Journal: Cardiovascular Diabetology 
Abstract: Background The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. Methods Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG). Hearts and plasma were isolated for biochemical approaches. Cultured cardiomyocytes were examined for receptor distribution after incretin stimulation in high fatty acid or high glucose media. Results Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18FDG assimilation and diastolic dysfunction. However, sitagliptin improved hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced 18FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal translocation of the glucose transporter-4 (Glut4), in detriment of the fatty acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal translocation were also increased after GLP-1 stimulation in high-fatty acid incubated cardiomyocytes. PI3K/Akt and AMPKα were involved in this response. Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar effects. Conclusions Besides of its anti-hyperglycemic effect, sitagliptin-enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by shifting fatty acid to glucose utilization in the cardiomyocyte, and thus, improving cardiac efficiency and reducing lipolysis.
URI: http://hdl.handle.net/10553/51221
ISSN: 1475-2840
DOI: 10.1186/s12933-017-0643-2
Source: Cardiovascular Diabetology [ISSN 1475-2840], v. 17(12)
Appears in Collections:Artículos
Show full item record

Google ScholarTM

Check

Altmetric


Share



Export metadata



Items in accedaCRIS are protected by copyright, with all rights reserved, unless otherwise indicated.