3,5-diiodothyronine (3,5-T2) reduces blood glucose independently of insulin sensitization in obese mice

Author(s)

da Silva Teixeira, S. ; Filgueira, C. ; Sieglaff, D. H. ; Benod, C. ; Villagomez, R. ; Minze, L. J. ; Zhang, A. ; Webb, P. ; Nunes, M. T.

• Document type: Journal article
• Source: ACTA PHYSIOLOGICA; v. 220, n. 2, p. 238-250, JUN 2017.
• Web of Science Citations: 18

Abstract

AimThyroid 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. MethodsCell- 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. ResultsT3 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. Conclusions3,5-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. (AU)

• FAPESP's process: 10/18151-7 - Characterization of actions of TH and its agonist GC-1 in the homeostasis glycemic: study in muscle cells and diabetic rats
• Grantee: Silvania da Silva Teixeira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/17430-5 - Characterization of actions of T3 in the homeostasis glycemic
• Grantee: Silvania da Silva Teixeira
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 13/05629-4 - Genomic vs nongenomic actions of thyroid hormones: changes of paradigms, physiological implications and therapeutical perspectives
• Grantee: Maria Tereza Nunes
• Support Opportunities: Research Projects - Thematic Grants