Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: role of GLP-1 isoforms in Glut4 receptor trafficking

Figures

• 

  Fig. 1. Sitagliptin reduced hyperglycemia and glucose intolerance in GK rats. a Body weight and plasma parameters were evaluated in the experimental model. TG, triglycerides; Ch, cholesterol, LDL and HDL, low- and high-density lipoproteins, respectively, and FFA, free FA. N = 10, each group. b Plasma glucose, insulin and GLP-1 were measured in fasting rats before (0 min) and after (15–60 min) an oral glucose loading (G). *p < 0.05 and **p < 0.01 vs. wistar. †p < 0.05 and ††p < 0.01 vs. GK rats. §p < 0.05 vs. 15 min glucose-overload or fasting state. N = 7, each group

• 

  Fig. 2. Sitagliptin improved myocardial glucose uptake and mitigated myocardial dysfunction in GK rats. a Left, cardiac PET images (sagittal, coronal and axial slices) of [18F]-FDG metabolism in (A) wistar, (B) GK and (C) GK-treated rats. Color scale bars represent the standardized uptake value (SUV) range in the myocardia. Right, quantification of SUV in the animal model. b The left-ventricular posterior wall (LVPW) and inter-ventricular septum (IVS) thicknesses, left-ventricular diastolic and systolic diameters (LVDD and LVSD, respectively), the ejection fraction (EF), deceleration time, and the E/A ratio were measured in the rats. Representative Echo-Doppler images for each group are also shown (top). *p < 0.05 and **p < 0.01 vs. wistar. †p < 0.05 and ††p < 0.01 vs. GK rats. N = 8, each group

• 

  Fig. 3. Sitagliptin enhanced cardiac Glut4 in detriment of FAT/CD36 in GK rats. a Glut4, d Glut1 and e FAT/CD36 protein levels in cytosolic (c) and sarcolemmal (s) fractions from wistar, GK and GK-sitagliptin myocardia. b Glut4 and f FAT/CD36 mRNA expression in the model. c phospho-Akt473 (dotted bars) and phospho-AMPKα496 (plain bars) protein expression in these hearts. *p < 0.05 and **p < 0.01 vs. cytosolic isoform or wistar rats. †p < 0.05 vs. GK rats or sarcolemmal isoform in wistar. N = 8, each group

• 

  Fig. 4. GLP-1 and GLP-1(9-36) increased endosomal and sarcolemmal Glut4 in hyperlipidemic cardiomyocytes. Glut4 expression in endosome- (e) and sarcolemmal (s)-enriched fractions of a HG- and b HF-stimulated C2C12. Some cells were pre-treated with GLP-1 or GLP-1(9-36). *p < 0.05 vs. endosome. †p < 0.05 and ∂p < 0.05 vs. sarcolemmal. §p < 0.05 vs. endosome from HF-incubated cells. c Sarcolemmal (left) and endosome (right) Glut4 expression was detected in Wortmannin pre-incubated GLP-1-stimulated cardiomyocytes, under HF medium. *p < 0.05 vs. HF, †p < 0.05 vs. HF + GLP-1. d Left, Glut4 mRNA expression after HF incubation (1–12 h). Right, Glut4 mRNA expression after 12 h HF stimulation and/or GLP-1 or GLP-1(9-36). *p < 0.05 and **p < 0.01 vs. control. †p < 0.05 vs. HF-incubated cells

• 

  Fig. 5. Sitagliptin reduced FA-delivery and FAO mediators in GK rats. Protein expression of a FABP3, c PPARα, GPAT1, SPTLC2 and d PDK4 in wistar, GK and GK-sitagliptin treated myocardia. b mRNA expression of CPT1b mitochondrial transporter and ACADl and ACADm FAO enzymes. *p < 0.05 and **p < 0.01 vs. wistar. †p < 0.05 vs. GK. N = 8, each group