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Exercise mediated protection of diabetic heart through modulation of microRNA mediated molecular pathways
Jason Kar Sheng Lew1, James T Pearson2,3, Daryl O Schwenke4
1Department of Physiology, HeartOtago, University of Otago, 270, Great King Street, Dunedin, 9010, New Zealand.
Abstract:
Hyperglycaemia, hypertension, dyslipidemia and insulin resistance collectively impact on the myocardium of people with diabetes, triggering molecular, structural and myocardial abnormalities. These have been suggested to aggravate oxidative stress, systemic inflammation, myocardial lipotoxicity and impaired myocardial substrate utilization. As a consequence, this leads to the development of a spectrum of cardiovascular diseases, which may include but not limited to coronary endothelial dysfunction, and left ventricular remodelling and dysfunction. Diabetic heart disease (DHD) is the term used to describe the presence of heart disease specifically in diabetic patients. Despite significant advances in medical research and long clinical history of anti-diabetic medications, the risk of heart failure in people with diabetes never declines. Interestingly, sustainable and long-term exercise regimen has emerged as an effective synergistic therapy to combat the cardiovascular complications in people with diabetes, although the precise molecular mechanism(s) underlying this protection remain unclear. This review provides an overview of the underlying mechanisms of hyperglycaemia- and insulin resistance-mediated DHD with a detailed discussion on the role of different intensities of exercise in mitigating these molecular alterations in diabetic heart. In particular, we provide the possible role of exercise on microRNAs, the key molecular regulators of several pathophysiological processes.
Insights
Diabetic heart disease involves molecular changes in the heart. Regular exercise may protect against these changes, potentially through microRNA regulation, offering a synergistic therapy for diabetic cardiovascular complications.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Diabetes mellitus is associated with significant cardiovascular complications, including diabetic heart disease (DHD).
- Hyperglycemia, insulin resistance, and associated metabolic dysfunctions trigger molecular and structural myocardial abnormalities.
- Despite advances, heart failure risk in diabetic patients remains high, necessitating novel therapeutic strategies.
Purpose of the Study:
- To review the mechanisms underlying hyperglycemia- and insulin resistance-mediated DHD.
- To discuss the role of exercise intensity in mitigating molecular alterations in the diabetic heart.
- To explore the potential role of exercise in modulating microRNAs in DHD.
Main Methods:
- Literature review focusing on molecular mechanisms of DHD.
- Analysis of studies investigating exercise interventions in diabetic models.
- Examination of research on microRNA regulation in cardiovascular pathophysiology.
Main Results:
- Hyperglycemia and insulin resistance induce oxidative stress, inflammation, lipotoxicity, and impaired substrate utilization in the myocardium.
- These factors contribute to left ventricular remodeling, dysfunction, and coronary endothelial dysfunction.
- Exercise, particularly sustainable regimens, shows promise in counteracting these detrimental effects.
Conclusions:
- Diabetic heart disease arises from complex molecular pathways driven by hyperglycemia and insulin resistance.
- Exercise emerges as a crucial synergistic therapy for managing cardiovascular risks in diabetes.
- MicroRNAs represent a potential molecular target for exercise-mediated cardioprotection in diabetic patients.
