Circadian rhythms, insulin action, and glucose homeostasis.

Abstract

Accumulating evidence supports a role for the circadian clock in the development of metabolic disease. We discuss the influence of the circadian clock on glucose homeostasis, intermediary factors in this relationship, and potential therapies for the prevention or attenuation of metabolic disease associated with circadian misalignment. Murine studies with tissue-specific deletion of core clock genes in key metabolic tissues confirm a mechanistic relationship between the circadian clock and the development of metabolic disease. Circadian misalignment increases insulin resistance and decreases pancreatic function. Clock gene polymorphisms or altered expression of clock genes induced by circadian misalignment appear to play a role in the development of obesity and diabetes in humans. Circadian disruption caused by exposure to light at night is associated with lower nocturnal melatonin, which in turn seems to affect glucose metabolism. Potential therapies for circadian misalignment include entraining the central pacemaker with timed light exposure and/or melatonin and restricting food intake to the biological day. Completing the understanding of how genetic and environmental factors influence the circadian clock and the effect these have on human circadian metabolic physiology and disease will allow us to develop therapies for treating and preventing associated metabolic disease.