The role of circadian clock-related genes in skeletal muscle insulin resistance and type 2 diabetes

• Grant number: 22/05957-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: November 01, 2022
• End date: October 31, 2023
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Vitor Rosetto Muñoz
• Supervisor: Carl Ronald Kahn
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Harvard University, Boston, United States
• Associated to the scholarship: 21/08692-5 - Analysis of the rev-erb-alpha protein interactome through immunoprecipitation of target protein and identification of possible ligands by mass spectrometry in cell culture, BP.PD

Abstract

Insulin resistance is a major risk factor for type 2 diabetes (T2D) and metabolic syndrome. Environmental factors, such as feeding patterns and physical activity levels, can favor insulin resistance development. However, in some cases, skeletal muscle insulin sensitivity alterations can occur many years before changes in glucose tolerance. In addition, induced pluripotent stem cells (iPSC) from T2D or insulin-resistant subjects keep the disease characteristics even after being differentiated into myoblasts (iMyos). Thus, cell-autonomous mechanisms may have an essential role in substrate metabolization and, consequently, whole-body physiology and homeostasis. Previous transcriptomic data from Dr. Kahn's lab showed important changes in circadian rhythm-related genes in iMyos from T2D subjects. These data corroborate the findings obtained in our laboratory and previous data from the literature. The manipulation of genes involved with circadian rhythm can have an expressive effect on skeletal muscle insulin sensitivity. Therefore, we will use cutting-edge and updated technology in molecular biology to understand how these clock-related genes could be associated with insulin sensitivity in skeletal muscle cells. (AU)