Epigenetic mechanisms involved in insulin resistance in skeletal muscle of obese Wistar rats and type 2 diabetic goto-kakizaki rats

• Grant number: 21/07063-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2021
• End date: September 30, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Sandro Massao Hirabara
• Grantee: Natalia Pagliusi Martins
• 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

Peripheral insulin resistance and inflammation accompany the development of type 2 diabetes mellitus (DM2), with a high prevalence in obese patients. However, a high percentage of lean 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 non-obese. The causes associated with the development of DM2, especially in lean individuals, still remain to be fully elucidated. Recent studies indicate the involvement of different microRNAs (miRs) in the development of insulin resistance in skeletal muscle, although the molecular mechanisms are not completely known. Thus, this project will investigate the role of different miRs in insulin resistance in the skeletal muscle of diet-induced obese Wistar rats and Goto-Kakizaki (GK) diabetic rats (a lean DM2 model). Molecular mechanisms will be analyzed by determining the expression of key proteins involved in insulin signaling (Akt and GSK), glucose metabolism (GLUT-4, phosphofructokinase, and citrate synthase), and by analyzing potential miRs involved in this process (miR-17, miR-29a, miR-29b, miR-106b, miR-27a, miR-30d, and miR-135a). Thus, this project will be important to identify potential miRs as molecular therapeutic targets involved in insulin resistance in skeletal muscle in obese Wistar and lean GK type 2 diabetic rats, aiming to direct future studies for the development of therapies to prevent and/or treat muscle insulin resistance and related diseases, including obesity, type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. (AU)