Circadian clocks and insulin resistance

• Published in: Nature reviews. Endocrinology Vol. 15; no. 2; pp. 75 - 89
• Main Authors: Stenvers, Dirk Jan, Scheer, Frank A. J. L., Schrauwen, Patrick, la Fleur, Susanne E., Kalsbeek, Andries
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-02-2019; Nature Publishing Group
• Subjects: 631/378/1385/1330; 631/443/319/1642/137/773; 631/80/105; 692/163/2743/2037; Adipose tissue; Animals; Blood Glucose - analysis; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Clock gene; Complications and side effects; Development and progression; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Drug Administration Schedule; Eating - physiology; Endocrinology; Energy expenditure; Energy Metabolism - physiology; Food intake; Glucose; Glucose - metabolism; Health aspects; Humans; Hypothalamus; Insulin; Insulin - administration & dosage; Insulin Resistance; Insulin secretion; Liver; Mammals; Medicine; Medicine & Public Health; Mice; Morbidity; Pancreas; Physiological aspects; Review Article; Risk factors; Secretion; Sleep and wakefulness; Suprachiasmatic nucleus; Type 2 diabetes; Netherlands
• ISSN: 1759-5029; 1759-5037
• DOI: 10.1038/s41574-018-0122-1

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.
Insulin resistance is a main determinant in the development of type 2 diabetes mellitus. Here, the authors review the physiological links between circadian clocks and insulin sensitivity and present current evidence for a relationship between circadian disruption and insulin resistance.
Key points
The circadian timing system consists of a central brain clock in the hypothalamic suprachiasmatic nucleus and peripheral clocks in tissues, including the liver, muscle, adipose tissue and pancreas.
Misalignment between different components of the circadian timing system and daily rhythms of sleep–wake behaviour and food intake might contribute to the development of insulin resistance.
Strategies to improve metabolic health by circadian synchrony include modulating light exposure, modulating rhythmic behaviour and chronotherapy.
Circadian molecules are a promising new treatment option for insulin resistance.