Timed Inhibition of Orexin System by Suvorexant Improved Sleep and Glucose Metabolism in Type 2 Diabetic db/db Mice.

Sleep disturbances are associated with type 2 diabetes; therefore, the amelioration of sleep may improve metabolic disorders. To investigate this possibility, we here examined the effects of suvorexant, an antiinsomnia drug targeting the orexinsystem, on sleep and glucose metabolism in type 2 diabetic mice. Diabetic db/db mice had a longer wakefulness time during the resting period, as compared with nondiabetic db/m+ control mice. The single or 7-day administration of suvorexantat lights-on (ie, the beginning of the resting phase) increased nonrapid eye movement sleep time during the resting phase and, as a consequence, reduced awake time. The daily resting-phase administration of suvorexantfor 2–4 weeks improved impaired glucose tolerancein db/db mice without affecting body weight gain, food intake, systemic insulin sensitivity, or serum insulin, and glucagon levels. No changes were detected in the markers of lipid metabolism and inflammation, such as the hepatic triglyceride content and Tnf-α mRNA l...