Regulation of insulin resistance in the soleus muscle of non-obese Goto-Kakizaki type2 diabetic rats by bone marrow transplantation

• Grant number: 24/07646-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Sandro Massao Hirabara
• Grantee: Karolayne Oliveira Souza
• Host Institution: Centro de Ciências Biológicas e da Saúde. 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

Insulin resistance (IR) and inflammation accompany the development of type 2 diabetes mellitus (DM2), with a high prevalence in obese patients. However, a high percentage of non-obese individuals have DM2, especially in certain regions. For example, in Brazil, the percentage reaches 10% to 20%, while in Japan, around 60% of patients with DM2 are not obese. The causes associated with the development of DM2, especially in the latter case, remain to be elucidated, however studies demonstrate that chronic hyperglycemia is capable of promoting epigenetic changes, changing the cellular phenotype to a constant pro-inflammatory one. Recent studies indicate that bone marrow transplantation can alleviate insulin resistance, although the molecular mechanisms are not completely understood at this time. Therefore, this project will investigate the role of bone marrow transplantation in the context of insulin resistance in the soleus muscle (predominantly oxidative muscle) of GK rats (DM2 model, non-obese). The molecular mechanisms will be analyzed using the Western Blotting technique by determining the expression of key proteins involved in insulin signaling (Akt and GSK-3) in glucose uptake and metabolism (GLUT-4, phosphofructokinase and citrate synthase), and the The inflammatory profile will be analyzed by pro-inflammatory cytokines (IL-1² and TNF-±) and the gene expression of GLUT-4, phosphofructokinase-1 and citrate synthase using the qPCR technique (real-time PCR). With this, we intend to identify potential molecular therapeutic targets involved in insulin resistance in the soleus muscle in GK rats (lean type 2 diabetics) and its modulation by bone marrow transplantation, with the aim of directing future studies aimed at developing therapies aimed at prevention. and/or treatment of this disorder and related diseases, especially in type 2 diabetes mellitus without obesity.