Piromelatine, a novel melatonin receptor agonist, stabilizes metabolic profiles and ameliorates insulin resistance in chronic sleep restricted rats

Chronic sleep deprivation may speed the onset or increase the severity of age-related conditions such as Type 2 diabetes, high blood pressure and obesity. Piromelatine (Neu-P11) is a novel melatonin agonist, which has been developed for the treatment of insomnia. Animal studies have suggested possible efficacy of piromelatine in sleep maintenance, anxiety and depression. In addition, piromelatine has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFSD) rats. The objective of this study was to investigate the effects of piromelatine on insulin sensitivity in sleep restricted rats. Sleep restriction was established by rotating cages intermittently for 20 h thereby sleeping time of rats was limited to 4 h per day. During 8 days of sleep restriction, rats were injected intraperitoneally with piromelatine (20 mg/kg), melatonin (5 mg/kg) or a vehicle. The results showed that sleep restriction increased plasma glucose, fasting insulin, total cholesterol (TC), triglycerides (TG) and oxidative stress markers while HDL-cholesterol (HDL-C) level and glucose tolerance were decreased. However, under piromelatine or melatonin treatment, the levels of plasma glucose, TG, TC decreased and HDL-C, glucose tolerance and antioxidative potency increased when compared with the vehicle-treated group. These data suggest that chronic sleep restriction in rats induce metabolic dysfunction, oxidative stress and insulin resistance, and these symptoms were improved by treatment with piromelatine or melatonin. We conclude that piromelatine could regulate metabolic profiles and insulin sensitivity, and attenuate insulin resistance induced by sleep restriction. (C) 2014 Elsevier B.V. All rights reserved