Characterization of actions of T3 in the homeostasis glycemic

• Grant number: 12/17430-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): January 10, 2013
• Effective date (End): January 09, 2014
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Silvania da Silva Teixeira
• Supervisor: Paul Webb
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Houston Methodist Research Institute (HMRI), United States
• Associated to the scholarship: 10/18151-7 - Characterization of actions of TH and its agonist GC-1 in the homeostasis glycemic: study in muscle cells and diabetic rats, BP.PD

Abstract

Thyroid hormones (TH) regulated the expression of genes. Among the various roles of TH are the metabolic function and our main interest is specifically related to the metabolism of carbohydrates and lipids. It is a well-known fact that TH stimulate the expression of enzymes of glycolytic and oxidative pathways, accelerating the metabolism of glucose. Furthermore, TH increase the expression of the SLC2A4 gene, which encodes the GLUT4, the key glucose transporter of skeletal muscle, heart and adipose tissues. However in the states of hyper and hypothyroidism alterations in glucose homeostasis indicative of insulin resistance have been reported. As for the lipid metabolism there is evidence that TH exert lipolytic effects by increasing the sensitivity of adipose tissue to catecholamines, as well as reducing the concentration of cholesterol in plasma. The set of data presented here shows that some function of TH, if encouraged, could bring important contributions to the maintenance of glucose homeostasis, unlike other function that compromises it. Accordingly, our results showed that chronic treatment with T3 increased insulin sensitivity in diabetic mice and decreased their blood glucose. Considering these results, this study aims to identify in diabetic animals treated with T3 for a four-week period (1) the TH receptor isoforms involved (2) determine what tissues are used by T3 to control glucose homeostasis and (3) evaluate the molecular mechanisms used by the T3 to promote the improvement of glucose homeostasis. Although the use of T3 as a therapeutic agent is quite unfeasible in this experimental condition (diabetes), to identify the receptor involved as well as the molecular mechanisms by which it acts, could result in specific agonists or antagonists being produced and used as future therapeutic strategies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA TEIXEIRA, S.; FILGUEIRA, C.; SIEGLAFF, D. H.; BENOD, C.; VILLAGOMEZ, R.; MINZE, L. J.; ZHANG, A.; WEBB, P.; NUNES, M. T.. 3,5-diiodothyronine (3,5-T2) reduces blood glucose independently of insulin sensitization in obese mice. ACTA PHYSIOLOGICA, v. 220, n. 2, p. 238-250, JUN 2017. (10/18151-7, 12/17430-5, 13/05629-4)