SKELETAL MUSCLE ATROPHY IN GOTO-KAKIZAKI RATS BY SUSPENSION OF THE HIND LEGS

• Grant number: 23/02376-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Rui Curi
• Grantee: Victor Matheus Rodrigues Coelho
• 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

Type 2 diabetes mellitus (DM2) patients exhibit peripheral insulin resistance, usually triggered by excess body mass. However, about 15% of DM2 diabetic patients are not obese, and in Japan, it reaches 60%, a condition reproduced in Goto-Kakizaki (GK) rats. These animals spontaneously exhibit insulin resistance in early life. Musculoskeletal disorders are highly prevalent in diabetic patients. The imbalance between the synthesis and degradation of proteins leads to a loss of muscle mass that affects patients' quality of life with DM2. Another factor that exacerbates muscle mass loss is the disuse of skeletal muscles when patients are bedridden or immobilized in conditions such as hospitalization. A 72-hour rest period results in a loss of 14 to 17% of skeletal muscle mass. The molecular mechanisms and hormonal changes that regulate the loss of muscle mass due to disuse in patients with T2DM are still unclear. This study aims to investigate the molecular mechanisms and hormonal changes involved in signaling protein synthesis and degradation in EDL and soleus muscles through induction of atrophy by suspension of the hind legs for 7 days in GK rats. The hypothesis to be tested is that non-obese rats with type 2 diabetes (GK) have more significant loss of skeletal muscle mass after disuse due to hind leg suspension than control animals. Characterizing the mechanisms involved will allow identifying strategies to attenuate skeletal muscle mass loss in diabetes.