Role of the integrin-linked kinase/TGF-/SMAD pathway in sitagliptin-mediated cardioprotective effects in a rat model of diabetic cardiomyopathy

Objectives Diabetic cardiomyopathy is a known complication of diabetes mellitus. Herein, we aimed to determine whether glycemic control mediated by sitagliptin, a dipeptidyl peptidase-4 inhibitor, can ameliorate diabetic myocardial abnormalities by modulating TGF-beta signaling via the SMAD and integrin-linked kinase (ILK) pathways.Methods Four groups of male Wistar albino rats were used, with six rats in each group. Two nondiabetic and two diabetic (produced by a single intraperitoneal dose of streptozotocin (55 mg/kg)) groups were administered either normal saline or sitagliptin (100 mg/kg) orally for 6 weeks. Subsequently, HW/BW ratios and cardiac enzymes were assessed, along with a histological examination of cardiac tissues. Levels of TGF-beta, collagen I, p-SMAD2/3, TNF-alpha, MMP-9, and ILK were detected.Results Compared with the diabetic control group, sitagliptin-treated diabetic rats exhibited considerably reduced HW/BW ratios and troponin I and creatine kinase-MB levels, with improvements in histopathological changes in cardiac tissues. TGF-beta, collagen I, p-SMAD2/3, TNF-alpha, and MMP-9 levels were significantly decreased in the sitagliptin-treated diabetic group, whereas ILK was elevated following sitagliptin treatment.Conclusion Sitagliptin could afford cardioprotective effects for the first time by altering ILK-associated TGF-beta/SMAD signaling pathways. Thus, sitagliptin may be a promising therapeutic target for the prevention of diabetic cardiomyopathy.