Zhang, Zhe, Wang, Xing, Yang, Linlin, Yang, Linquan, Ma, Huijuan. (1400). Liraglutide ameliorates myocardial damage in experimental diabetic rats by inhibiting pyroptosis via Sirt1/AMPK signaling. , 24(10), 1358-1365. doi: 10.22038/ijbms.2021.56771.12677
Zhe Zhang; Xing Wang; Linlin Yang; Linquan Yang; Huijuan Ma. "Liraglutide ameliorates myocardial damage in experimental diabetic rats by inhibiting pyroptosis via Sirt1/AMPK signaling". , 24, 10, 1400, 1358-1365. doi: 10.22038/ijbms.2021.56771.12677
Zhang, Zhe, Wang, Xing, Yang, Linlin, Yang, Linquan, Ma, Huijuan. (1400). 'Liraglutide ameliorates myocardial damage in experimental diabetic rats by inhibiting pyroptosis via Sirt1/AMPK signaling', , 24(10), pp. 1358-1365. doi: 10.22038/ijbms.2021.56771.12677
Zhang, Zhe, Wang, Xing, Yang, Linlin, Yang, Linquan, Ma, Huijuan. Liraglutide ameliorates myocardial damage in experimental diabetic rats by inhibiting pyroptosis via Sirt1/AMPK signaling. , 1400; 24(10): 1358-1365. doi: 10.22038/ijbms.2021.56771.12677

Liraglutide ameliorates myocardial damage in experimental diabetic rats by inhibiting pyroptosis via Sirt1/AMPK signaling

Iranian Journal of Basic Medical Sciences
دوره 24، شماره 10، دی 2021، صفحه 1358-1365    اصل مقاله (1.8 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2021.56771.12677
نویسندگان
Zhe Zhang1؛ Xing Wang1؛ Linlin Yang1؛ Linquan Yang1؛ Huijuan Ma* 1، 2
1Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang 050051, P.R. China
2Department of Endocrinology, Hebei General Hospital, Shijiazhuang 050051, P.R. China
چکیده
Objective(s): Liraglutide, a well-established drug for treating diabetes mellitus (DM), has recently gained attention for its cardiovascular benefits in diabetes via multiple cellular activities; however, whether liraglutide improves myocardial damage by inhibiting pyroptosis and the mechanisms of these potential effects remain unknown.
Materials and Methods: In this study, high-fat diet feeding and low-dose streptozotocin (STZ) injection were used to construct a rat DM model. Rats with fasting blood glucose (FBG) levels >16.7 mmol/l received subcutaneous injections of liraglutide (0.2 mg/kg) for 4 weeks. Metabolic parameters, the heart weight/body weight (HW/BW) ratio, and histopathology were examined. Protein levels of inflammatory, pyroptosis, and NOD-like receptor protein 3 (NLRP3) inflammasome markers were assessed via Western blotting. In in vitro studies, a sirtuin 1 (Sirt1) inhibitor (EX 527, 200 nM) and an AMP-activated protein kinase (AMPK) inhibitor (compound C, 20 µM) were used to inhibit Sirt1 and AMPK pathways, respectively.
Results: Liraglutide significantly attenuated cardiac hypertrophy, pathological changes, inflammation, pyroptosis, and NLRP3 inflammasome activation, accompanied by increased Sirt1 and AMPK activation. Consistent with the in vivo results, liraglutide attenuated high glucose (HG)-induced pyroptosis and NLRP3 inflammasome activation along with enhanced Sirt1 and AMPK activation. After blockade of Sirt1 and AMPK signaling, the protective effect of liraglutide was restrained. Notably, EX 527 abolished the stimulatory effect of liraglutide on Sirt1 and AMPK signaling, whereas compound C blunted AMPK signaling without affecting Sirt1 signaling. 
Conclusion: Liraglutide may protect against myocardial damage by activating the Sirt1/AMPK signaling pathways to inhibit cellular pyroptosis in DM.
کلیدواژه‌ها
Cardiovascular disease؛ Diabetes mellitus؛ Inflammasomes؛ Rats؛ Sirtuin 1
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