Circadian clocks and insulin resistance

Abstract

Insulin resistance is a main determinant in the development of type 2 diabetes mellitus and a major cause of morbidity and mortality. The circadian timing system consists of a central brain clock in the hypothalamic suprachiasmatic nucleus and various peripheral tissue clocks. The circadian timing system is responsible for the coordination of many daily processes, including the daily rhythm in human glucose metabolism. The central clock regulates food intake, energy expenditure and whole-body insulin sensitivity, and these actions are further fine-tuned by local peripheral clocks. For instance, the peripheral clock in the gut regulates glucose absorption, peripheral clocks in muscle, adipose tissue and liver regulate local insulin sensitivity, and the peripheral clock in the pancreas regulates insulin secretion. Misalignment between different components of the circadian timing system and daily rhythms of sleep-wake behaviour or food intake as a result of genetic, environmental or behavioural factors might be an important contributor to the development of insulin resistance. Specifically, clock gene mutations, exposure to artificial light-dark cycles, disturbed sleep, shift work and social jet lag are factors that might contribute to circadian disruption. Here, we review the physiological links between circadian clocks, glucose metabolism and insulin sensitivity, and present current evidence for a relationship between circadian disruption and insulin resistance. We conclude by proposing several strategies that aim to use chronobiological knowledge to improve human metabolic health.