Abstract
In order for the heart to maintain its continuous mechanical work and provide the systolic movement to uphold coronary blood flow, substantial synthesis of adenosine triphosphate (ATP) is required. Under normal conditions cardiac tissue utilizes roughly 70% fatty acids (FA), and 30% glucose for the production of ATP; however, during impaired metabolic conditions like insulin resistance and diabetes glucose metabolism is dysregulated and FA account for 99% of energy production. One of the major consequences of a shift in FA metabolism in cardiac tissue is an increase in reactive oxygen species (ROS) and lipotoxicity, which ultimately lead to mitochondrial dysfunction. Thyroid hormones (TH) have direct effects on cardiac function and glucose metabolism during impaired metabolic conditions suggesting that TH may improve glucose metabolism in an insulin resistant condition. None‐classical TH signaling in the heart has shown to phosphorylate protein kinase B (Akt) and increase activity of phosphoinositide‐3‐kinase (PI3K), which are critical mediators in the insulin‐stimulated glucose uptake pathway. Studies on peripheral tissues such as skeletal muscle and adipocytes have demonstrated TH treatment improved glucose intolerance in a diabetic model and increased insulin‐regulated glucose transporter (GLUT4) mRNA levels. GLUT4 is a downstream target of thyroid response element (TRE), which demonstrates that THs regulate glucose via GLUT4. Elevated 3,5,3′‐triiodothyronine (T3) increased glucose oxidation rate and decreased the glycolytic intermediate, fructose 6‐phosphate (F6P) in cardiomyocytes, in addition to increasing mitochondrial biogenesis and pyruvate transport across the mitochondrial membrane. These findings along with a few other studies on T3 treatment in cardiac tissue suggest TH may improve glucose metabolism in an insulin resistant model and ameliorate the effects of diabetes and metabolic syndrome. This review highlights the potential benefits of exogenous TH on ameliorating metabolic dysfunction in the heart.
Highlights
In order for the heart to maintain its continuous mechanical work and provide the systolic movement to uphold coronary blood flow, substantial synthesis of adenosine triphosphate (ATP) is required
One of the major consequences of a shift in fatty acids (FA) metabolism in cardiac tissue is an increase of reactive oxygen species (ROS) and lipotoxicity, which lead to mitochondrial dysfunction
The heart demands a constant supply of energy to maintain its continuous mechanical work and provide the systolic movement to maintain systemic and pulmonary blood flow
Summary
PubMed, Google Scholar, the California Digital Library, and the American Journal of Physiology (AJP) were searched using a combination of the following terms: “thyroid hormone,” “T4,” “T3,” “diabetic cardiomyopathy,” “insulin resistance,” “type 2 diabetes,” “metabolic syndrome,” “metabolism,” “glucose metabolism,” “glucose oxidation,” “glycolysis,” “glucose uptake,” “GLUT4,” and “insulin signaling.” Primary and review articles were the main sources used for this review. Hepatic G6P, which is the rate-limiting step in glycolysis, is reduced; treatment with T4 rescued this effect These data demonstrate the potential for THs to contribute to glucose metabolism via different pathways, helping to ameliorate some of glycolytic and oxidative impairments associated with insulin resistance in the liver. TH activity contributes to efficiency of cardiac contractility by activating the expression of myosin 6, and promoting mitochondrial biogenesis, mitochondrial protein synthesis, and increasing pyruvate transfer across mitochondrial membrane These results in cardiac tissue along with previous studies on peripheral tissues suggest that TH have the potential to improve glucose metabolism by increasing glucose oxidation, glycogenolysis, and glucose uptake in cardiomyocytes during insulin resistance and the potential for TH to ameliorate diabetic cardiomyopathy. Correlating the changes in these variables to cardiac function would be especially important to understand the functional relevance of how the changes in substrate metabolism alters function and the potential for exogenous TH to ameliorate the impairments induced by metabolic defects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
