Vildagliptin and caloric restriction for cardioprotection in pre-diabetic rats

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   Figure 1

   The experimental protocol of the study. HFCR, high-fat diet treated with CR diet; HFCRVil, high-fat diet treated with CR diet and vildagliptin; HFD, high-fat diet; HFV, high-fat diet treated with vehicle; HFVil, high-fat diet treated with vildagliptin; HPLC, high-performance liquid chromatography; MDA, Malondialdehyde; MMP, mitochondrial membrane potential; ND, normal diet; NDV, normal diet treated with vehicle; OGTT, oral glucose tolerance test; P–V loop, pressure–volume loop; ROS, reactive oxygen species.
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   Figure 2

   The effects of HFD consumption, HFCR, vildagliptin, and combined HFCR and vildagliptin on HRV and echocardiographic parameters. (A) HRV and (B) % fractional shortening (%FS) in ND and HFD rats at baseline and week 12. *P < 0.05 vs ND (independent sample t-test, n = 6 for ND group and n = 12 for HFD group). (C) HRV and (D) %FS in ND and HFD rats treated with vehicle, calorie restriction (CR), vildagliptin and CR combined vildagliptin. *P < 0.05 vs NDV, ^†P < 0.05 vs HFV, ^‡P < 0.05 vs HFCR, ^#P < 0.05 vs HFCR (1-WAY ANOVA, LSD post hoc test, n = 6 per subgroups). HFCR, high-fat diet treated with CR diet; HFCRVil, high-fat diet treated with CR diet and vildagliptin; HFD, high-fat diet; HF, high frequency; HFV, high-fat diet treated with vehicle; HFVil, high-fat diet treated with vildagliptin; HRV, heart rate variability; LF, low frequency; ND, normal diet; NDV, normal diet treated with vehicle.
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   Figure 3

   The effects of HFCR, vildagliptin and combined HFCR and vildagliptin on plasma FGF21 levels, FGFR1/β-Klotho receptors complex and intracellular Erk1/2 expression and phosphorylation. (A) Plasma FGF21 levels at weeks 12, (B) plasma FGF21 levels post treatment, (C) p-FGFR1, (D) t-FGFR1, (E) p-FGFR1/t-FGFR1, (F) β-Klotho, (G) p-Erk1/2, (H) t-Erk1/2, and (I) p-Erk1/2/t-Erk1/2 ratio in ND and HFD rats treated with vehicle, Calorie restriction (CR), vildagliptin, and CR combined with vildagliptin. *P < 0.05 vs NDV, ^†P < 0.05 vs HFV, ^‡P < 0.05 vs HFCR (1-WAY ANOVA, LSD post hoc test, n = 4–6 per subgroups). Erk1/2, extracellular signal-regulated protein kinases 1 and 2; FGFR1, fibroblast growth factor receptors 1; HFCR, high-fat diet treated with CR diet; HFCRVil, high-fat diet treated with CR diet and vildagliptin; HFD, high-fat diet; HFV, high-fat diet treated with vehicle; HFVil, high-fat diet treated with vildagliptin; ND, normal diet; NDV, normal diet treated with vehicle; p-FGFR1, phospho FGFR1; p-ERK1/2, phospho ERK1/2; t-ERK1/2, total ERK1/2.
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   Figure 4

   Effects of HFCR, vildagliptin and combined HFCR and vildagliptin on intracellular FGF21 signaling pathways including anti-apoptosis and fatty acid oxidation pathways. (A) Bax, (B) BCL-2, (C) Bax/BCL-2 ratio, (D) Cleaved Caspase-3/t-Caspase-3 ratio, (E) PGC-1α, and (F) CPT-1 in ND and HFD rats treated with vehicle, Caloric restriction (CR), vildagliptin, and CR combined vildagliptin. *P < 0.05 vs NDV, ^†P < 0.05 vs HFV, ^‡P < 0.05 vs HFCR (1-WAY ANOVA, LSD post hoc test, n = 4–6 per subgroups). CPT1, carnitine palmitoyltransferase 1; HFCR, high-fat diet treated with CR diet; HFCRVil, high-fat diet treated with CR diet and vildagliptin; HFD, high-fat diet; HFV, high-fat diet treated with vehicle; HFVil, high-fat diet treated with vildagliptin; ND, normal diet; NDV, normal diet treated with vehicle; PGC-1α, proliferator-activated receptor gamma coactivator 1-alpha.
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   Figure 5

   Effects of HFCR, vildagliptin and combined HFCR and vildagliptin on cardiac mitochondrial function and cardiac mitochondria morphology. (A) Cardiac mitochondrial ROS production, (B) red/green fluorescent intensity ratio, (C) Cardiac mitochondrial swelling, and (D) Cardiac mitochondria morphology by transmission electron microscope (TEM) in ND and HFD treated with vehicle, CR, vildagliptin, and CR combined with vildagliptin. *P < 0.05 vs NDV, ^†P < 0.05 vs HFV, ^‡P < 0.05 vs HFCR (1-WAY ANOVA, LSD post hoc test, n = 6 per subgroups). HFCR, high-fat diet treated with CR diet; HFCRVil, high-fat diet treated with CR diet and vildagliptin; HFD, high-fat diet; HFV, high-fat diet treated with vehicle; HFVil, high-fat diet treated with vildagliptin; ND, normal diet; NDV, normal diet treated with vehicle; ROS, reactive oxygen species.

• © 2017 Society for Endocrinology