Role of pro-inflammatory cytokines in triggering hypothyroidism in experimental Diabetes Mellitus. Effect of T3 and insulin treatment

• Grant number: 23/05869-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2023
• End date: December 27, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Guilherme Rondi Fernandes
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Diabetes Mellitus (DM) is the main metabolic disease nowadays, being characterized by hyperglycemia resulting either from the lack of insulin or from peripheral resistance to its action. In addition to a chronic subclinical inflammation that is well studied in the literature and responsible for several deleterious effects, DM also courses with thyroid dysfunction, being the hypothyroidism the most prevalent, whose cause is still little known. Previous studies have already shown a positive correlation between hypothyroidism and DM, however restricting themselves to explaining such cross-talk only by an autoimmune point of view. However, there are evidences that other factors are also at play, as evidenced by recent studies by our group, which detected a primary hypothyroidism even in alloxan-induced DM rats. It is therefore necessary that we investigate other possibilities for understanding the cause(s) of thyroid dysfunction in DM, which is responsible for several deleterious effects. To this end, the present study aims to assess whether there is a correlation between chronic subclinical inflammation and the development of hypothyroidism in DM.Male Wistar rats (250 g) will be induced to DM1 through the administration of alloxan (150 mg/kg, ip) and subdivided in five groups: (1) DM: treated with saline, ip, 0,9%; (2) T3: treated with T3 (1,5 µg/100 g BW, ip); (3) I6: treated with insulin sc (6U, repository dose); (4) I3: treated with insulin sc (3U) and (5) T3I3: treated with T3 (1,5 µg/100 g BW, ip) and insulin sc (3U). The treatment will be carried out for 4 weeks. After euthanasia, it will be assessed in the thyroid the expression of the cytokines TNF-±, IL-10 and the transcriptional factor NF-ºBp65, as well as of the important markers of thyroid function thyroperoxidase (TPO) and sodium-iodide cotransporter (NIS). Serum TSH concentration, glycosylated hemoglobin (HbA1c) and the rate of glucose decay (KITT) will be also evaluated. Non-diabetic animals will be used as the control group.