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Insulin Signaling and Heart Failure
Christian Riehle1, E Dale Abel2
1From the Division of Endocrinology and Metabolism, Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City.
Circulation Research
|April 2, 2016
Summary
Heart failure is linked to insulin resistance, impacting cardiac metabolism and function. Understanding these complex insulin signaling changes in the heart is crucial for developing new therapeutic strategies.
Area of Science:
- Cardiology
- Endocrinology
- Molecular Biology
Background:
- Heart failure (HF) is strongly associated with generalized insulin resistance.
- Insulin-resistant states like type 2 diabetes mellitus (T2DM) and obesity elevate HF risk, independent of traditional risk factors.
- Altered systemic and neurohumoral environments in insulin resistance impact cardiac metabolism and signaling.
Purpose of the Study:
- To review the intricate mechanisms of insulin signaling within the myocardium.
- To elucidate how these pathways are dysregulated in HF and insulin-resistant conditions.
- To discuss the therapeutic implications of these myocardial insulin signaling alterations.
Main Methods:
- Review of existing literature on insulin signaling in the heart.
- Analysis of molecular and cellular changes in cardiomyocytes during HF.
- Examination of the impact of T2DM and obesity on cardiac insulin pathways.
Main Results:
- Insulin resistance affects both proximal and distal insulin signaling in cardiomyocytes.
- Activation of proximal pathways may drive adverse left ventricular remodeling and mitochondrial dysfunction.
- Repression of distal pathways, including forkhead box O (FOXO) signaling, impairs cardiac metabolism and function.
Conclusions:
- Dysregulated myocardial insulin signaling is a key feature of heart failure.
- Altered insulin pathways contribute to cardiac dysfunction, metabolic impairment, and structural changes.
- Targeting these specific insulin signaling defects may offer novel therapeutic avenues for HF prevention and treatment.
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