Effects of the resistance training on skeletal muscle in a non-obese animal model of type 2 diabetes mellitus

• Grant number: 25/02820-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2025
• End date: April 30, 2026
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Sandro Massao Hirabara
• Grantee: Érika Pereira Santos
• Host Institution: Centro de Ciências Biológicas e da Saúde. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic multifactorial syndrome of epidemic proportions, characterized by insulin resistance and inflammation, leading to hyperglycemia. Although the causes of T2DM are not yet fully understood, factors such as obesity, hypercaloric diets rich in carbohydrates and fats, and increased adiposity contribute to cellular alterations associated with a constant subclinical pro-inflammatory state and reduced insulin sensitivity. Despite being frequently associated with obesity, a significant proportion of individuals with T2DM do not present excess weight, although the pathogenesis of this process requires further study. In T2DM, metabolism and insulin response are impaired in various tissues, including skeletal muscle, resulting in dysfunction and muscle mass loss, although the mechanisms are not yet fully elucidated. The Goto-Kakizaki rat has been used as an experimental model of non-obese T2DM, showing similarities to the human model. Studies suggest that resistance training can reduce insulin resistance, improve glycemic control and lipid profile, and enhance muscle mass and function, highlighting its potential protective and/or therapeutic effect in diabetes models. This project aims to evaluate the glucose metabolism, insulin resistance, and inflammation in the glycolytic triceps muscle from Goto-Kakizaki rats submitted to a resistance training protocol. The molecular mechanisms will be investigated through the quantification of muscle glycogen and triglycerides, as well as the analysis of proteins involved in insulin signaling (IRS, AKT, GSK3, and GLUT4) and protein synthesis and degradation (mTOR, S6K, MAFbx, and MURF-1) via Western Blotting. The inflammatory profile will be assessed by quantifying pro-inflammatory cytokines (TNF-¿, IL-10, and IL-1¿) and anti-inflammatory cytokines (IL-4, IL-6, and IL-1ra), while metabolism will be analyzed through the gene expression of citrate synthase (CS) and phosphofructokinase (PFK-1) via RT-PCR. Thus, this study will contribute to understanding how metabolism, insulin response, and inflammation are altered in skeletal muscle in non-obese T2DM, as well as the potential beneficial impact of resistance training, providing insights for future approaches in disease prevention and/or treatment. (AU)