Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome  

作　　者：Gu-Lao Zhang Yuan Liu Yan-Feng Liu Xian-Tao Huang Yu Tao Zhen-Huan Chen Heng-Li Lai 

机构地区：[1]Department of Cardiology,Jiangxi Provincial People's Hospital,The First Affiliated Hospital of Nanchang Medical College,Nanchang 330000,Jiangxi Province,China

出　　处：《World Journal of Diabetes》2024年第4期724-734,共11页世界糖尿病杂志（英文版）（电子版）

基　　金：Supported by National Natural Science Foundation of China,No.82000276;the Science and Technology Project of Jiangxi Provincial Health Commission,No.202310005.

摘　　要：BACKGROUND Diabetic cardiomyopathy(DCM),which is a complication of diabetes,poses a great threat to public health.Recent studies have confirmed the role of NLRP3(NOD-like receptor protein 3)activation in DCM development through the inflammatory response.Teneligliptin is an oral hypoglycemic dipeptidyl peptidase-IV inhibitor used to treat diabetes.Teneligliptin has recently been reported to have anti-inflammatory and protective effects on myocardial cells.AIM To examine the therapeutic effects of teneligliptin on DCM in diabetic mice.METHODS Streptozotocin was administered to induce diabetes in mice,followed by treatment with 30 mg/kg teneligliptin.RESULTS Marked increases in cardiomyocyte area and cardiac hypertrophy indicator heart weight/tibia length reductions in fractional shortening,ejection fraction,and heart rate;increases in creatine kinase-MB(CK-MB),aspartate transaminase(AST),and lactate dehydrogenase(LDH)levels;and upregulated NADPH oxidase 4 were observed in diabetic mice,all of which were significantly reversed by teneligliptin.Moreover,NLRP3 inflammasome activation and increased release of interleukin-1βin diabetic mice were inhibited by teneligliptin.Primary mouse cardiomyocytes were treated with high glucose(30 mmol/L)with or without teneligliptin(2.5 or 5μM)for 24 h.NLRP3 inflammasome activation.Increases in CKMB,AST,and LDH levels in glucose-stimulated cardiomyocytes were markedly inhibited by teneligliptin,and AMP(p-adenosine 5‘-monophosphate)-p-AMPK(activated protein kinase)levels were increased.Furthermore,the beneficial effects of teneligliptin on hyperglycaemia-induced cardiomyocytes were abolished by the AMPK signaling inhibitor compound C.CONCLUSION Overall,teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

关 键 词：Diabetic cardiomyopathy Teneligliptin NLRP3 AMPK INTERLEUKIN-1Β 

分 类 号：R587.2[医药卫生—内分泌] R542.2[医药卫生—内科学]