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

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)