Aerobic interval training almost completely restored the contractile function and Ca2+ handling of diabetic cardiomyocytes to levels close to sedentary wild type mice.
Does 13 weeks of aerobic interval training improve cardiomyocyte Ca2+ cycling and excitation-contraction coupling in a mouse model of type-2 diabetes?
Aerobic interval training normalizes cardiomyocyte contractile function and calcium handling in diabetic mice without altering systemic glucose or insulin levels.
RATIONALE: In the present study we explored the mechanisms behind excitation-contraction (EC) coupling defects in cardiomyocytes from mice with type-2 diabetes (db/db). OBJECTIVE: We determined whether 13 weeks of aerobic interval training could restore cardiomyocyte Ca(2+) cycling and EC coupling. METHODS AND RESULTS: Reduced contractility in cardiomyocytes isolated from sedentary db/db was associated with increased diastolic sarcoplasmic reticulum (SR)-Ca(2+) leak, reduced synchrony of Ca(2+) release, reduced transverse (T)-tubule density, and lower peak systolic and diastolic Ca(2+) and caffeine-induced Ca(2+) release. Additionally, the rate of SR Ca(2+) ATPase-mediated Ca(2+) uptake during diastole was reduced, whereas a faster recovery from caffeine-induced Ca(2+) release indicated increased Na(+)/Ca(2+)-exchanger activity. The increased SR-Ca(2+) leak was attributed to increased Ca(2+)-calmodulin-dependent protein kinase (CaMKIIdelta) phosphorylation, supported by the normalization of SR-Ca(2+) leak on inhibition of CaMKIIdelta (AIP). Exercise training restored contractile function associated with restored SR Ca(2+) release synchronicity, T-tubule density, twitch Ca(2+) amplitude, SR Ca(2+) ATPase and Na(+)/Ca(2+)-exchanger activities, and SR-Ca(2+) leak. The latter was associated with reduced phosphorylation of cytosolic CaMKIIdelta. Despite normal contractile function and Ca(2+) handling after the training period, phospholamban was hyperphosphorylated at Serine-16. Protein kinase A inhibition (H-89) in cardiomyocytes from the exercised db/db group abolished the differences in SR-Ca(2+) load when compared with the sedentary db/db mice. EC coupling changes were observed without changes in serum insulin or glucose levels, suggesting that the exercise training-induced effects are not via normalization of the diabetic condition. CONCLUSIONS: These data demonstrate that aerobic interval training almost completely restored the contractile function of the diabetic cardiomyocyte to levels close to sedentary wild type.
Stølen et al. (Thu,) conducted a other in Diabetic cardiomyopathy in type-2 diabetes (db/db) mice. Aerobic interval training vs. Sedentary db/db mice was evaluated on Cardiomyocyte contractile function and Ca2+ cycling. Aerobic interval training almost completely restored the contractile function and Ca2+ handling of diabetic cardiomyocytes to levels close to sedentary wild type mice.
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