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- Title
Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling.
- Authors
Pei, Haifeng; Qu, Yan; Lu, Xiaoyan; Yu, Qiujun; Lian, Kun; Liu, Peilin; Yan, Wenjun; Liu, Jingyi; Ma, Yanzhuo; Liu, Yi; Li, Chengxiang; Li, Weijie; Lau, Wayne; Zhang, Haifeng; Tao, Ling
- 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.
- Subjects
ADIPONECTIN; CORONARY disease; CORONARY heart disease treatment; REPERFUSION injury; PEOPLE with diabetes; LABORATORY mice; CELLULAR signal transduction; INSULIN resistance
- Publication
Basic Research in Cardiology, 2013, Vol 108, Issue 1, p1
- ISSN
0300-8428
- Publication type
Article
- DOI
10.1007/s00395-012-0322-0