Zhang GL, Liu Y, Liu YF, Huang XT, Tao Y, Chen ZH, Lai HL. Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome. World J Diabetes 2024; 15(4): 724-734 [PMID: 38680706 DOI: 10.4239/wjd.v15.i4.724]
Corresponding Author of This Article
Heng-Li Lai, MD, Chief Physician, Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Aiguo Road, Donghu District, Nanchang 330000, Jiangxi Province, China. laihengli@163.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Basic Study
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Zhang GL, Liu Y, Liu YF, Huang XT, Tao Y, Chen ZH, Lai HL. Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome. World J Diabetes 2024; 15(4): 724-734 [PMID: 38680706 DOI: 10.4239/wjd.v15.i4.724]
Gu-Lao Zhang, Yuan Liu, Yan-Feng Liu, Xian-Tao Huang, Yu Tao, Zhen-Huan Chen, Heng-Li Lai, Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330000, Jiangxi Province, China
Co-corresponding authors: Zhen-Huan Chen and Heng-Li Lai.
Author contributions: Zhang GL, Chen ZH, Lai HL designed the research study; Liu Y, Liu YF, Huang XT performed the research; Zhang GL, Chen ZH, Tao Y, and Lai HL analyzed the data and wrote the manuscript; all authors have read and approve the final manuscript. Lai HL and Chen ZH contributed equally to this work as co-corresponding authors. They made equally important contributions in the process of design, submission and revision, and interpreted all the research data.
Supported byNational Natural Science Foundation of China, No. 82000276; and the Science and Technology Project of Jiangxi Provincial Health Commission, No. 202310005.
Institutional animal care and use committee statement: The study was reviewed and approved by the Jiangxi Provincial People's Hospital Institutional Review Board (Approval No. KT089).
Conflict-of-interest statement: All the Authors declare that they have no conflicts of interest related to this manuscript.
Data sharing statement: The data are available on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Corresponding author: Heng-Li Lai, MD, Chief Physician, Department of Cardiology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Aiguo Road, Donghu District, Nanchang 330000, Jiangxi Province, China. laihengli@163.com
Received: October 8, 2023 Peer-review started: October 8, 2023 First decision: December 6, 2023 Revised: December 20, 2023 Accepted: February 27, 2024 Article in press: February 27, 2024 Published online: April 15, 2024 Processing time: 186 Days and 14.5 Hours
ARTICLE HIGHLIGHTS
Research 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.
Research motivation
This study examined the therapeutic effects of teneligliptin on DCM in diabetic mice.
Research objectives
Teneligliptin improves DCM by means of NLRP3, providing a new target for teneligliptin in the treatment of DCM.
Research methods
Streptozotocin (STZ) was administered to induce diabetes in mice, followed by treatment with 30 mg/kg teneligliptin. Small animal ultrasonic apparatus was used to measure mice heart function, The levels of creatine kinase-MB (CK-MB), aspartate transaminase (AST), lactate dehydrogenase (LDH), and interleukin (IL)-1β were detected by ELISA, cardiomyocytes areas were measured by HE staining, Real-time PCR was used to measure NOX-4 mRNA expression, western blot was used to measure NOX-4, NLRP3, caspase-1, AMPK, p-AMPK protein expression level, primary cardiomyocytes was isolated in neonatal mice. The data are presented as the mean ± SD and were analyzed using one-way analysis of variance with GraphPad Prism software 6.0. P < 0.05 was considered to indicate a statistically significant difference.
Research results
Marked increases in cardiomyocyte area and heart weight/tibia length; reductions in fractional shortening, ejection fraction, and heart rate; increases in CK-MB, AST, and 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 IL-1β in diabetic mice were inhibited by teneligliptin. Primary mouse cardiomyocytes were treated with high glucose (30 mmol/L) with or without teneligliptin (2.5 or 5 µM) for 24 h. NLRP3 inflammasome activation and the increases in CK-MB, 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.
Research conclusions
Overall, teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.
Research perspectives
Our study suggests that in future clinical work, teneligliptin may treat diseases involving the NLRP3 pathway.
