Abstract:Aim To investigate the effect of Neu-P11, a novel melatonin receptor agonist, on insulin sensitivity in sleep restricted rats as well as the underlying mechanism. Methods Method of rotating cage was adopted to establish SD rat models of sleep restriction. During the 8 days of sleep restriction, rats were injected intraperitoneally with Neu-P11 (20 mg/kg), MLT (5 mg/kg), saline respectively every day. Plasma glucose, fasting insulin, malondialdehyde (MDA) levels and enzyme activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) were detected at the end of experiment, the proteins of JNK and phosphorylated JNK in muscles were measured by Western blot. Results Compared with control group, sleep restricted rats showed increased levels of plasma glucose, fasting insulin, but antioxidative potency decreased. However, in Neu-P11 and melatonin-treated sleep restricted rats, the levels of plasma glucose, fasting insulin and MDA decreased with an increase of SOD, GSH-Px activities. Neu-P11 or melatonin also down-regulated the levels of JNK and phosphorylated JNK which were increased by sleep restriction. These data suggest that glucose homeostasis and antioxidative potency of the chronic sleep restricted rats were protected by Neu-P11 and melatonin. Conclusions Neu-P11 could improve metabolic profiles and insulin resistant induced by sleep restriction, and the regulation of JNK and antioxidative potency may be the underlying mechanism.