Gene expression and cytokine secretion related to T lymphocyte differentiation during insulin resistance development in Goto-Kakizaki rats

• Grant number: 19/10118-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2019
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Renata Gorjao
• Grantee: Ana Carolina Gomes Pereira
• Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
• Associated research grant: 18/09868-7 - Cellular and molecular mechanisms of insulin resistance and inflammation in obese Wistar rats and lean Goto-Kakizaki rats: causes and associations with diet and physical exercise, AP.TEM

Abstract

Peripheral insulin resistance (RI) and type 2 Diabetes mellitus (DM2) have a high prevalence in obese patients. However, there is an elevated number of non-obese patients that have DM2. The causes associated with the development of DM2 and the characterization of the immunological response in these cases are not clear. Goto-Kakizaki (GK) rats develop genetically well defined condition of RI and DM2 without obesity. The aim of this study is to investigate the changes in expression of genes related with differentiation of T lymphocytes and production of cytokines by these cells during type 2 diabetes mellitus development in Goto-Kakizaki rats. Initially, lymphocytes will be isolated from the mesenteric lymph nodes of the animals at the end of weaning and after two and four months of age, followed by the evaluation of the following parameters: 1) Peripheral insulin resistance (glucose tolerance and insulin tests); 2) lymphocyte cytokine production (IL-2, IL-10, IL-4, IL-6, IL-17, IFN-gamma and TNF-alpha) in cells cultured with PMA and Ionomycin; 3) percentage of T regulatory (CD4+, CD25+ and Foxp3+), Th1 (CD4+, INF-gama+), Th2 (CD4+, IL-4) and Th17 (CD4+, IL-17) cells after stimulation with PMA and ionomycin; 3) mRNA expression of IL-35, TGF-², Foxp3, Tbet, ROR-gt, GATA3 and Blimp-1. Studies related to mechanisms involved with the process of T lymphocytes differentiation associated to DM2 genesis without the chronic effects of obesity are important for the scientific improvement of this pathology knowledge.