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 20h thereby sleeping time of rats was limited to 4h per day. During 8 days of sleep restriction, rats were injected intraperitoneally with
piromelatine (20mg/kg),
melatonin (5mg/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.