title: 3,5-diiodothyronine (3,5-T2) reduces blood glucose independently of insulin sensitization in obese mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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 nor 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.
  
  
  
  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.
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.|Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: S
authors: S
authors: da Silva Teixeira
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: C
authors: C
authors: Filgueira
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: D H
authors: DH
authors: Sieglaff
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: C
authors: C
authors: Benod
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: R
authors: R
authors: Villagomez
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: L J
authors: LJ
authors: Minze
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: A
authors: A
authors: Zhang
authors: Genomic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
authors: P
authors: P
authors: Webb
authors: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors: M T
authors: MT
authors: Nunes
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D059305:Diet, High-Fat; D004104:Diiodothyronines / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D004104:Diiodothyronines; D014284:Triiodothyronine; C030103:3,5-diiodothyronine; C030629:3,3'-diiodothyronine
keywords: blood glucose; diiodothyronine; insulin response; metabolism; thyroid hormone; thyromimetic