title: Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling.
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.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changlexi Road, Xi'an 710032, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Pei
authors.forename: Yan
authors.initials: Y
authors.lastname: Qu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.forename: Qiujun
authors.initials: Q
authors.lastname: Yu
authors.forename: Kun
authors.initials: K
authors.lastname: Lian
authors.forename: Peilin
authors.initials: P
authors.lastname: Liu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yan
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Yanzhuo
authors.initials: Y
authors.lastname: Ma
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Chengxiang
authors.initials: C
authors.lastname: Li
authors.forename: Weijie
authors.initials: W
authors.lastname: Li
authors.forename: Wayne Bond
authors.initials: WB
authors.lastname: Lau
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D052242:Adiponectin / Q000097:blood / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology*; D013311:Streptozocin
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D055372:AMP-Activated Protein Kinases