Effect of sitagliptin on cardiomyocyte pyroptosis induced by type 2 diabetes mellitus and underlying mechanism |
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Authors: | XU Jie YANG Ling ZHANG Meng ZHU Min-hang XIE Fen JIN Xiao-xia YUAN Qiong ZHOU Qian-yi |
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Affiliation: | New Drug Innovation Institute, School of Medicine, Wuhan University of Science and Technology, Hubei Provincial Key Laboratory of Occupational Hazard Identification and Control, Wuhan 430065, China |
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Abstract: | AIM: To explore the effect of sitagliptin (SLT) on cardiomyocyte pyroptosis induced by type 2 diabetes mellitus (T2DM) and the underlying mechanism. METHODS: The T2DM rat model was established by high-fat diet and intraperitoneal injection of streptozotocin (35 mg/kg). The model rats were treated with SLT at 3, 10 and 30 mg/kg and nicotinamide[NAM; an non-specific inhibitor of sirtuin (SIRT) family] at 500 mg/kg for 4 weeks. Fasting blood glucose was measured, and the tissue proteins were determined by the methods of Western blot and immunochemistry. RESULTS: Compared with control group, the pyroptosis of cardiomyocytes and NLRP3 expression were significantly induced, while the protein level of SIRT3 was downregulated by T2DM (P<0.05). SLT inhibited the pyrpotosis of diabetic rat cardiomyocytes, downregulated the expression of NLRP3, and upregulated the expression of SIRT3 in a dose-dependent manner (P<0.05). All the function of SLT (30 mg/kg) was reversed by the treatment with NAM (500 mg/kg). Compared with control group, the pyroptosis of cardiomyocytes and NLRP3 expression were significantly induced, while the protein level of SIRT3 was not regulated by NAM (500 mg/kg). CONCLUSION: SLT exerts the inhibitory effect on the pyroptosis of cardiomyocytes induced by diabetes, and the mechanism is related to the SIRT3/NLRP3 signaling pathway. |
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Keywords: | Type 2 diabetes mellitus Diabetic cardiomyopathy Sitagliptin Pyroptosis SIRT3/NLRP3 signaling pathway |
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