Cardiac expression of human type 2 iodothyronine deiodinase increases glucose metabolism and protects against doxorubicin-induced cardiac dysfunction in male mice
Authors
Hong, Eun-GyoungKim, Brian W.
Jung, Dae Young
Kim, Jong Hun
Yu, Tim
Seixas Da Silva, Wagner
Friedline, Randall H.
Bianco, Suzy D.
Seslar, Stephen P.
Wakimoto, Hiroko
Berul, Charles I.
Russell, Kerry S.
Lee, Ki Won
Larsen, P. Reed
Bianco, Antonio C.
Kim, Jason K.
UMass Chan Affiliations
Division of Endocrinology, Metabolism, and Diabetes, Department of MedicineProgram in Molecular Medicine
Document Type
Journal ArticlePublication Date
2013-10-01Keywords
AMP-Activated Protein KinasesAnimals
Antibiotics, Antineoplastic
Doxorubicin
Glucose
Glucose Clamp Technique
Glucose Transporter Type 1
Heart Ventricles
Humans
*Insulin Resistance
Iodide Peroxidase
Lipid Metabolism
Liver
Male
Mice
Mice, Transgenic
Proto-Oncogene Proteins c-akt
Survival Analysis
Triiodothyronine
Ventricular Dysfunction
induced
Cardiology
Cellular and Molecular Physiology
Endocrinology
Endocrinology, Diabetes, and Metabolism
Metadata
Show full item recordAbstract
Altered glucose metabolism in the heart is an important characteristic of cardiovascular and metabolic disease. Because thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in T3 using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the alpha-myosin heavy chain promoter (MHC-D2). Hyperinsulinemic-euglycemic clamps showed normal whole-body glucose disposal but increased hepatic insulin action in MHC-D2 mice as compared to wild-type (WT) littermates. Insulin-stimulated glucose uptake in heart was not altered, but basal myocardial glucose metabolism was increased by more than two-fold in MHC-D2 mice. Myocardial lipid levels were also elevated in MHC-D2 mice, suggesting an overall up-regulation of cardiac metabolism in these mice. The effects of doxorubicin (DOX) treatment on cardiac function and structure were examined using M-mode echocardiography. DOX treatment caused a significant reduction in ventricular fractional shortening and resulted in more than 50% death in WT mice. In contrast, MHC-D2 mice showed increased survival rate after DOX treatment, and this was associated with a six-fold increase in myocardial glucose metabolism and improved cardiac function. Myocardial activity and expression of AMPK, GLUT1, and Akt were also elevated in MHC-D2 and WT mice following DOX treatment. Thus, our findings indicate an important role of thyroid hormone in cardiac metabolism and further suggest a protective role of glucose utilization in DOX-mediated cardiac dysfunction.Source
Endocrinology. 2013 Oct;154(10):3937-46. doi: 10.1210/en.2012-2261. Link to article on publisher's siteDOI
10.1210/en.2012-2261Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30211PubMed ID
23861374Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1210/en.2012-2261