Insulin receptor substrate signaling controls cardiac energy metabolism and heart failure

被引:82
作者
Guo, Cathy A. [1 ]
Guo, Shaodong [1 ]
机构
[1] Texas A&M Univ, Dept Nutr & Food Sci, Coll Agr & Life Sci, College Stn, TX 77843 USA
基金
美国国家卫生研究院; 美国食品与农业研究所;
关键词
insulin resistance; heart failure; insulin receptor substrates; forkhead transcription factor Foxo1; PROTEIN-KINASE B; TRANSCRIPTION FACTORS; GENE-EXPRESSION; BLOOD-PRESSURE; UP-REGULATION; GROWTH; MICE; RESISTANCE; PHOSPHORYLATION; SENSITIVITY;
D O I
10.1530/JOE-16-0679
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The heart is an insulin-dependent and energy-consuming organ in which insulin and nutritional signaling integrates to the regulation of cardiac metabolism, growth and survival. Heart failure is highly associated with insulin resistance, and heart failure patients suffer from the cardiac energy deficiency and structural and functional dysfunction. Chronic pathological conditions, such as obesity and type 2 diabetes mellitus, involve various mechanisms in promoting heart failure by remodeling metabolic pathways, modulating cardiac energetics and impairing cardiac contractility. Recent studies demonstrated that insulin receptor substrates 1 and 2 (IRS-1,-2) are major mediators of both insulin and insulin-like growth factor-1 (IGF-1) signaling responsible for myocardial energetics, structure, function and organismal survival. Importantly, the insulin receptor substrates (IRS) play an important role in the activation of the phosphatidylinositide-3-dependent kinase (PI-3K) that controls Akt and Foxo1 signaling cascade, regulating the mitochondrial function, cardiac energy metabolism and the renin-angiotensin system. Dysregulation of this branch in signaling cascades by insulin resistance in the heart through the endocrine system promotes heart failure, providing a novel mechanism for diabetic cardiomyopathy. Therefore, targeting this branch of IRS -> PI-3K -> Foxo1 signaling cascade and associated pathways may provide a fundamental strategy for the therapeutic and nutritional development in control of metabolic and cardiovascular diseases. In this review, we focus on insulin signaling and resistance in the heart and the role energetics play in cardiac metabolism, structure and function.
引用
收藏
页码:R131 / R143
页数:13
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