Moderate intensity exercise prevents diabetic cardiomyopathy associated contractile dysfunction through restoration of mitochondrial function and connexin 43 levels in db/db mice

作者：Veeranki Sudhakar^*; Givvimani Srikanth; Kundu Sourav; Metreveli Naira; Pushpakumar Sathnur; Tyagi Suresh C

来源：Journal of Molecular and Cellular Cardiology, 2016, 92: 163-173.

DOI：10.1016/j.yjmcc.2016.01.023

• Diabetes
• Obesity
• Exercise
• Mitochondrial-biogenesis
• Connexin
• Drp-1
• Mfn-2
• Cytochrome c
• Trans-membrane-potential
• Fibrosis

Aims: Although the cardiovascular benefits of exercise are well known, exercise induced effects and mechanisms in prevention of cardiomyopathy are less clear during obesity associated type-2 diabetes. The current study assessed the impact of moderate intensity exercise on diabetic cardiomyopathy by examining cardiac function and structure and mitochondrial function.
Methods: Obese-diabetic (db/db), and lean control (db/+) mice, were subjected to a 5 week, 300 m run on a tread-mill for 5 days/week at the speeds of 10-11 m/min. Various physiological parameters were recorded and the heart function was evaluated with M-mode echocardiography. Contraction parameters and calcium transits were examined on isolated cardiomyocytes. At the molecular level: connexin 43 and 37 (Cx43 and 37) levels, mitochondrial biogenesis regulators: Mfn2 and Drp-1 levels, mitochondrial trans-membrane potential and cytochrome c leakage were assessed through western blotting immunohistochemistry and flow cytometry. Ability of exercise to reverse oxygen consumption rate (OCR), tissue ATP levels, and cardiac fibrosis were also determined.
Results: The exercise regimen was able to prevent diabetic cardiac functional deficiencies: ejection fraction (EF) and fractional shortening (FS). Improvements in contraction velocity and contraction maximum were noted with the isolated cardiomyocytes. Restoration of interstitial and micro-vessels associated Cx43 levels and improved gap junction intercellular communication (GJIC) were observed. The decline in the Mfn2/Drp-1 ratio in the db/db mice hearts was prevented after exercise. The exercise regimen further attenuated transmembrane potential decline and cytochrome c leakage. These corrections further led to improvements in OCR and tissue ATP levels and reduction in cardiac fibrosis.
Conclusions: Moderate intensity exercise produced significant cardiovascular benefits by improving mitochondrial function through restoration of Cx43 networks and mitochondrial trans-membrane potential and prevention of excessive mitochondrial fission.

• 出版日期2016-3