Sitagliptin attenuates cardiomyopathy by modulating the JAK/STAT signaling pathway in experimental diabetic rats

Figures & data

Table 1 Effect of sitagliptin on BW, HW, and blood glucose in control and diabetic rats

	BW (g)		HW/BW ratio	Blood glucose (mg/dL)
	Baseline	90 days		Baseline	90 days
Control	166.92±4.49	269.60±6.58	0.39±0.02	95.40±4.85	93.66±4.47
Sitagliptin	150.33±5.89	296.51±9.71	0.40±0.16	99.74±3.71	93.49±4.75
Diabetic	161.20±3.77	142.10±6.62***	1.01±0.22**	307.00±11.45***	444.12±14.35***
Diabetic + sitagliptin	170.83±3.91	214.67±8.61#	0.48±0.06##	322.50±16.71	177.83±10.55###
F probability	>0.05	<0.001	<0.05	<0.001	<0.001

Notes: Data are mean ± SEM (N=8).

** P<0.01 and

*** P<0.001 for control and

# P<0.05,

## P<0.01, and

### P<0.001 for diabetic.

Abbreviations: BW, body weight; HW, heart weight; SEM, standard error of the mean.

Figure 1 Effect of sitagliptin on (A) troponin I level and (B) CK-MB activity.

Notes: Data are mean ± SEM (N=8). *P<0.05 and **P<0.01.
Abbreviations: CK-MB, creatine kinase MB; SEM, standard error of the mean.

Figure 2 Effect of sitagliptin on serum lipid profile and cardiovascular indices.

Notes: (A) Total cholesterol, (B) triglycerides, (C) LDL cholesterol, (D) vLDL cholesterol, (E) HDL cholesterol, (F) T cholesterol/HDL cholesterol, and (G) LDL cholesterol/HDL cholesterol. Data are mean ± SEM (N=8). ***P<0.001.
Abbreviations: HDL, high-density lipoprotein; LDL, low-density lipoprotein; SEM, standard error of the mean; T cholesterol, total cholesterol; vLDL, very low-density lipoprotein.

Figure 3 Effect of sitagliptin on oxidative stress and antioxidant defense system parameters.

Notes: (A) Malondialdehyde, (B) nitric oxide, (C) reduced glutathione, (D) superoxide dismutase, and (E) Catalase. Data are mean ± SEM (N=8). *P<0.05, **P<0.01, and ***P<0.001.
Abbreviations: CAT, catalase; GSH, reduced glutathione; MDA, malondialdehyde; NO, nitric oxide; SEM, standard error of the mean; SOD, superoxide dismutase.

Figure 4 Effect of sitagliptin on cardiac IL-6 levels.

Notes: Data are mean ± SEM (N=8). ***P<0.001.
Abbreviations: IL-6, interleukin-6; SEM, standard error of the mean.

Figure 5 Effect of sitagliptin on histological changes in the heart of control and diabetic rats.

Notes: Photomicrographs of H&E-stained heart sections of (A) control rats; (B) sitagliptin-treated rats showing normal heart tissue with normal features of myocardium cells, blood vessels, and endomysium; (C) diabetic rats revealing focal areas of myocardium degeneration (red arrow) and many myocardium cells degeneration (black arrow); and (D) sitagliptin-treated diabetic rats showing few myocardial cell degenerations (black arrow). Magnification ×400.
Abbreviation: H&E, hematoxylin and eosin.

Figure 6 Effect of sitagliptin on collagen deposition in the heart of control and diabetic rats.

Notes: Photomicrographs of Masson’s trichrome-stained heart sections of (A) control rats, (B) sitagliptin-treated rats showing normal distribution and normal amount of cardiac fibrous tissue (arrow), (C) diabetic rats showing large patches of strong fibrous tissue reactivity (arrow), and (D) sitagliptin-treated diabetic rats showing small patches of fibrous tissue (arrow). Magnification ×400.

Figure 7 Effect of sitagliptin on JAK2 phosphorylation in the heart of control and diabetic rats.

Notes: Photomicrographs of pJAK2-immunostained heart sections of (A) control rats, (B) sitagliptin-treated rats with the absence of immunopositive cytoplasm or nuclei (arrow), (C) diabetic rats showing strong immune reactivity of myocardium cells nuclei (arrows) and moderate immune reaction of the cytoplasm (arrow head), and (D) sitagliptin-treated diabetic rats showing few immunopositive nuclei (arrow). Magnification ×400.

Figure 8 Effect of sitagliptin on STAT3 phosphorylation in the heart of control and diabetic rats.

Notes: Photomicrographs of pSTAT3-immunostained heart sections of (A) control rats, (B) sitagliptin-treated rats showing the absence of immune positivity especially from the nuclei (arrow), (C) diabetic rats showing strong immune reactivity of almost all of myocardium cell nuclei and the endocardium endothelium cells (arrows), and (D) sitagliptin-treated diabetic rats showing many immunopositive nuclei of both endocardium endothelium and myocardium cells (arrows). Magnification ×400.