Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2024; 15(4): 724-734
Published online Apr 15, 2024. doi: 10.4239/wjd.v15.i4.724
Teneligliptin mitigates diabetic cardiomyopathy by inhibiting activation of the NLRP3 inflammasome
Gu-Lao Zhang, Yuan Liu, Yan-Feng Liu, Xian-Tao Huang, Yu Tao, Zhen-Huan Chen, Heng-Li Lai
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 by National 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.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
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
Abstract
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-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. 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.

CONCLUSION

Overall, teneligliptin mitigated DCM by mitigating activation of the NLRP3 inflammasome.

Keywords: Diabetic cardiomyopathy; Teneligliptin; NLRP3; AMPK; Interleukin-1β

Core Tip: Teneligliptin mitigated diabetic cardiomyopathy by mitigating the activation of NLRP3 (NOD-like receptor protein 3) inflammasome. Teneligliptin reversal markedly increased cardiomyocyte area and heart weight/tibia length, reduced fractional shortening, ejection fraction, and heart rate, increased creatine kinase-MB (CK-MB), aspartate transaminase (AST), and lactate dehydrogenase (LDH) levels, and upregulated NADPH oxidase 4 in streptozotocin-induced diabetic mice. Teneligliptin repressed activated NLRP3 inflammasome and increased CK-MB, AST, and LDH levels in glucose-stimulated cardiomyocytes, accompanied by an upregulation of phosphorylated-adenosine 5‘-monophosphate and activated protein kinase.