(589.2) Exogenous thyroxine increases GLUT4 translocation to the membrane in cardiomyocytes in insulin resistant OLETF rats Dora A Mendez1, Jose G. Soñanez-Organis2, Guillermo Vasquez-Anaya1, Daisuke Nakano3, Akira Nishiyama3, Rudy M Ortiz1 1Department of Molecular and Cell Biology, School of Natural Sciences, University of California, Merced, CA, USA 2Division of Science and Engineering, Department of Chemical Biological and Agropecuary Sciences, University of Sonora, Lazaro Cardenas 100, Colonia, Campus Navojoa, Francisco Villa, 85890 Navojoa, SON, Mexico 3Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan

Poster Board Number: E363

Dora Mendez (University of California), Jose Soñanez-Organis (University of Sonora), Guillermo Vasquez-Anaya (University of California), Daisuke Nakano (Kagawa University Medical School), Akira Nishiyama (Kagawa University Medical School), Rudy Ortiz (University of California)

During insulin resistance the heart undergoes a metabolic shift in which fatty acids (FA) accounts for about 99% of the ATP production. This metabolic shift is indicative of impaired glucose metabolism. A shift in FA metabolism with impaired glucose tolerance can cause an increase in reactive oxygen species (ROS) and lipotoxicity ultimately leading to impaired mitochondrial function. Thyroid hormones (TH) may improve glucose intolerance by increasing glucose reabsorption and metabolism in peripheral tissues but its effects on cardiac tissue during insulin resistance is not well known. The glucose transport protein, GLUT4, is a downstream target of the TH response element (TRE) indicating a possible mechanism by which THs regulate glucose metabolism. Non-classical TH signaling may also phosphorylate protein kinase B (Akt) and increase activity of phosphoinositide-3-kinase (PI3K), which are two key regulators in insulin-mediated glucose uptake. Insulin resistant, Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on glucose metabolism in cardiac tissue. Rats were assigned to four groups: 1) lean, Long Evans Tokushima Otsuka (LETO; n=6), 2) LETO + T4 (8 μg/100g BM/d × 5 wks; n=7), 3) untreated OLETF (n=6), and 4) OLETF + T4 (n=7). T4 increased GLUT4 gene expression by 85% (plt;0.05) in OLETF and increased GLUT4 protein translocation to the membrane by 328% (plt;0.05). Additionally, T4 increased phosphofructokinase-1 (PFK-1) gene expression, the rate limiting step in glycolysis, by 98% (plt;0.05) in OLETF. T4 increased AKT and p-AKT by 177% and 134% (plt;0.05), respectively, in LETO, but not in OLETF. The results suggest that increased T4 has the potential to increase glucose reabsorption and metabolism in the heart of insulin resistant rats to help restore impaired substrate metabolism.

DAM was supported by USDA HSI Educational Grant 2017-03691



Mean (±SE) percent change from LETO for GLUT4 in cardiac muscle of LETO, LETO + T4, OLETF, and OLETF+T4 after 5 wk treatment. *, P<0.05 vs. LETO. &, P<0.05 vs. OLETF. $, P<0.05 from OLETF + T4. #, P<0.05 from LETO + T4.