Circadian Regulation of Glucose Metabolism: Implications for Pathogenesis and Chronotherapy of Type 2 Diabetes

The global prevalence of type 2 diabetes continues to rise at an alarming pace, challenging existing strategies for disease prevention and management. Beyond traditional risk factors, increasing evidence indicates that glucose metabolism is temporally regulated by the body's 24 h biological clock and oscillates based on the time of day. Disturbances of the circadian clock function are linked to impairments in glucose homeostasis and increased risk of obesity and diabetes. This review explores the intricate relationship between the circadian system and glucose homeostatic control. We begin with an introduction to the hierarchical organization of the circadian system. Next, we examine the role of the circadian clock in regulating organs and tissues that are involved in glucose metabolism, i.e., the pancreas, skeletal muscles, the liver and adipose tissue. We next review evidence that supports the involvement of circadian disturbances in the pathogenesis of diabetes. Finally, we discuss chronotherapy and its potential application in clinical intervention of diabetes. As type 2 diabetes becomes increasingly common worldwide, understanding how the body's internal clock shapes this disease may open new and powerful opportunities for its prevention and treatment.