Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling.

Authors

• Haifeng Pei
• Yan Qu
• Xiaoyan Lu
• Qiujun Yu
• Kun Lian
• Peilin Liu
• Wenjun Yan
• Jingyi Liu
• Yanzhuo Ma
• Yi Liu
• Chengxiang Li
• Weijie Li
• Wayne Bond Lau
• Haifeng Zhang
• Ling Tao

Publication/Presentation Date

1-1-2013

Abstract

Type 1 diabetes (T1DM) portends poor prognosis concerning ischemic heart disease. Adiponectin (APN), an adipocytokine possessing insulin sensitizing and metabolic regulatory effects, has been recognized as a potent cardioprotective molecule. However, the relationship between APN and T1DM remains controversial and the role of cardiac-derived APN in T1DM is unclear. This study is aimed to investigate the dynamic change of both plasma and cardiac-derived APN expressions in T1DM, and the particular role of cardiac-derived APN in T1DM against myocardial ischemia/reperfusion (MI/R) injury. T1DM was established via intraperitoneal injection of streptozocin and followed by twice-daily subcutaneous injection of insulin or vehicle for 14 days. Non-diabetic mice of wild type and APN knockout were subjected to insulin or vehicle injection. MI/R was induced in Langendorff-perfused hearts. Compared to non-diabetic mice, plasma APN levels of diabetic mice significantly increased at 7 days, and slightly decreased at 14 days, while cardiac-derived APN levels gradually decreased over time. The MI/R injury measured as infarct size and cardiomyocyte apoptosis nearly doubled in diabetic mice. 14 days of insulin treatment increased both plasma and cardiac-derived APN levels in diabetic mice and attenuated myocardial injury via increasing AMPK phosphorylation in T1DM, which was partly reversed by Compound C (an AMPK inhibitor). Moreover, APN deficiency aggravated MI/R injury and partly abolished the protective effect of insulin treatment against MI/R injury, which was associated with decreased AMPK phosphorylation. The results suggest that cardiac-derived APN stimulated by long-term insulin treatment in T1DM exerts cardioprotection against MI/R injury via myocardial AMPK activation.

Volume

108

Issue

1

First Page

322

Last Page

322

ISSN

1435-1803

Published In/Presented At

Pei, H., Qu, Y., Lu, X., Yu, Q., Lian, K., Liu, P., Yan, W., Liu, J., Ma, Y., Liu, Y., Li, C., Li, W., Lau, W. B., Zhang, H., & Tao, L. (2013). Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling. Basic research in cardiology, 108(1), 322. https://doi.org/10.1007/s00395-012-0322-0

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

23262803

Department(s)

Administration and Leadership

Document Type

Article