Sleep Control, GPCRs, and Glucose Metabolism

Modern lifestyles prolong daily activities into the nighttime, disrupting circadian rhythms, which may cause sleep disturbances. Sleep disturbances have been implicated in the dysregulation of blood glucose levels and reported to increase the risk of type 2 diabetes (T2D) and diabetic complications. Sleep disorders are treated using anti-insomnia drugs that target ionotropic and G protein-coupled receptors (GPCRs), including γ-aminobutyric acid (GABA) agonists, melatonin agonists, and orexin receptor antagonists. A deeper understanding of the effects of these medications on glucose metabolism and their underlying mechanisms of action is crucial for the treatment of diabetic patients with sleep disorders. In this review we focus on the beneficial impact of sleep on glucose metabolism and suggest a possible strategy for therapeutic intervention against sleep-related metabolic disorders.

TrendsSleep disturbances are associated with increased risk for type 2 diabetes (T2D). Enhanced sympathetic tone, desynchronization of tissue circadian clocks, abnormal secretion of hormones, and obesity are relevant to insulin resistance during sleep disturbances.Melatonin regulates energy metabolism by maintaining circadian rhythms. Treatment with melatonin improves glucose metabolism by increasing insulin sensitivity in target tissues in T2D animals. Their beneficial effects in humans are controversial.γ-Aminobutyric acid (GABA) directly modulates insulin secretion from pancreatic islet β cells. The metabolic effects of GABA agonists/benzodiazepines on glucose metabolism remain controversial.Timely activation of the orexin system plays a crucial role in the maintenance of glucose homeostasis. Timely administration of orexin receptor antagonists might be beneficial for improving glucose intolerance in patients with sleep disorders.