TY - JOUR
T1 - 3,5-diodothyronine (3,5-T2) Reduces Blood Glucose Independently of Insulin Sensitization in Obese Mice
AU - Teixeira, Silvania da Silva
AU - Filgueira, Carly S.
AU - Sieglaff, Douglas H
AU - Benod, Cindy
AU - Villagomez, Rosa
AU - Minze, Laurie J
AU - Zhang, Aijun
AU - Webb, Paul
AU - Nunes, Maria Tereza
N1 - This article is protected by copyright. All rights reserved.
PY - 2016/10/22
Y1 - 2016/10/22
N2 - AIM: Thyroid hormones regulate metabolic response. While triiodothyronine (T3) is usually considered to be the active form of thyroid hormone, one form of diiodothyronine (3,5-T2) exerts T3-like effects on energy consumption and lipid metabolism. 3,5-T2 also improves glucose tolerance in rats and 3,5-T2 levels correlate with fasting glucose in humans. Presently, however, little is known about mechanisms of 3,5-T2 effects on glucose metabolism. Here, we set out to compare effects of T3, 3,5-T2 and another form of T2 (3,3-T2) in a mouse model of diet induced obesity and determined effects of T3 and 3,5-T2 on markers of classical insulin sensitization to understand how diiodothyronines influence blood glucose.METHODS: Cell and protein based assays of thyroid hormone action. Assays of metabolic parameters in mice. Analysis of transcript and protein levels in different tissues by qRT-PCR and western blot.RESULTS: T3 and 3,5-T2 both reduce body weight, adiposity and body temperature despite increased food intake. 3,3'-T2 lacks these effects. T3 and 3,5-T2 reduce blood glucose levels whereas 3,3'-T2 worsens glucose tolerance. Neither T3 or 3,5-T2 affects markers of insulin sensitization in skeletal muscle or white adipose tissue (WAT) but both reduce hepatic GLUT2 glucose transporter levels and glucose output. T3 and 3,5-T2 also induce expression of mitochondrial uncoupling proteins (UCPs) 3 and 1 in skeletal muscle and WAT, respectively.CONCLUSIONS: 3,5-T2 influences glucose metabolism in a manner that is distinct from insulin sensitization and involves reductions in hepatic glucose output and changes in energy utilization. This article is protected by copyright. All rights reserved.
AB - AIM: Thyroid hormones regulate metabolic response. While triiodothyronine (T3) is usually considered to be the active form of thyroid hormone, one form of diiodothyronine (3,5-T2) exerts T3-like effects on energy consumption and lipid metabolism. 3,5-T2 also improves glucose tolerance in rats and 3,5-T2 levels correlate with fasting glucose in humans. Presently, however, little is known about mechanisms of 3,5-T2 effects on glucose metabolism. Here, we set out to compare effects of T3, 3,5-T2 and another form of T2 (3,3-T2) in a mouse model of diet induced obesity and determined effects of T3 and 3,5-T2 on markers of classical insulin sensitization to understand how diiodothyronines influence blood glucose.METHODS: Cell and protein based assays of thyroid hormone action. Assays of metabolic parameters in mice. Analysis of transcript and protein levels in different tissues by qRT-PCR and western blot.RESULTS: T3 and 3,5-T2 both reduce body weight, adiposity and body temperature despite increased food intake. 3,3'-T2 lacks these effects. T3 and 3,5-T2 reduce blood glucose levels whereas 3,3'-T2 worsens glucose tolerance. Neither T3 or 3,5-T2 affects markers of insulin sensitization in skeletal muscle or white adipose tissue (WAT) but both reduce hepatic GLUT2 glucose transporter levels and glucose output. T3 and 3,5-T2 also induce expression of mitochondrial uncoupling proteins (UCPs) 3 and 1 in skeletal muscle and WAT, respectively.CONCLUSIONS: 3,5-T2 influences glucose metabolism in a manner that is distinct from insulin sensitization and involves reductions in hepatic glucose output and changes in energy utilization. This article is protected by copyright. All rights reserved.
U2 - 10.1111/apha.12821
DO - 10.1111/apha.12821
M3 - Article
C2 - 27770485
SN - 1748-1708
JO - Acta physiologica (Oxford, England)
JF - Acta physiologica (Oxford, England)
ER -