Catabolic and anabolic faces of insulin resistance and their disorders: a new insight into circadian control of metabolic disorders leading to diabetes

Abstract

Maintenance of glucose homeostasis during circadian behavioral cycles is critical. The processes controlling the switch between predominant lipolysis/fatty oxidation during fasting and predominant lipid storage/glucose oxidation following feeding are determined principally by insulin. Chronic elevated threshold of insulin resistance (IR) is a key pathological feature of obesity, Type 2 diabetes, sepsis and cancer cachexia; however, a temporal reduced threshold of IR is widely met in fasting/hibernation, pregnancy, antibacterial immunity, exercise and stress. Paradoxically, some of these cases are associated with catabolic metabolism, whereas others are related to anabolic pathways. This article considers the possible causes of circadian disorders in glucose and lipid metabolism that act as a driving force for obesity-promoted development of Type 2 diabetes. This is intended to provide improved insight into the pathogenesis of chronic circadian disorders that increase the risk of diabetes, and consider new targets for its metabolic and drug correction.