Neu-P11 Improves Insulin Resistance Caused By Sleep Restriction In SD Rats

Objective: We observed whether sleep restriction would cause insulin resistance, investigated whether the administration of the melatonin receptor agonist (Neu-P11) could improve insulin resistance, and studied the mechanism of Neu-P11 improving the insulin sensitivity caused by sleep restriction.Methods: 1. Group: 25 male Sprague Dawley rats were randomized assigned to five groups: Home cage controls (HC), sleep restriction groups (SR), sleep restriction Neu-P11-treating groups (SR-N), sleep restriction Mel-treating groups (SR-M), forced activity controls (FA). 2. Creation of sleep restriction model: The sleep restriction rats are subjected to a schedule of chronic sleep restriction that allowed 4h of sleep per day for 8 days. Sleep restriction is achieved by housing the rats in slowly rotating drums (3r/min) for 20h per day. Forced activity control rats walked twice the speed (6r/min) for half the time. These animals thus covered the same distance but had sufficient time to sleep. Each group is given intraperitoneal injection of Neu-P11 (20mg/kg), Mel (5mg/kg) or sodium chloride respectively. After the 8 days of sleep restriction, the rats were housed in home cages for 6 more days. The food consumed and the body weight of each rat is monitored every day. 3. Biochemical assay in blood serum: Glucose tolerance test (a glucose intragastric administration (20%)) is administered, blood samples are collected into capillary tubes after nicking the tip of the tail before, after the 8 days of sleep restriction and after the 6 days of recovery. Blood samples are collected into capillary tubes after nicking the tip of the tail. Glucose is analyzed by glucometer. Plasma samples are stored at -20°C until analyzed for insulin, TG, HDL-C and leptin. 4. After recovery, the rats were killed to obtain the skeletal muscles tissue. Western-blot were did to detect PI3K,P-PI3K,p70S6K and P-p70S6K.Results: 1. During the experiment period, the blood insulin and glucose level of sleep restriction groups rats increased significantly, glucose tolerance decreased significantly, the food intake increased significantly but no change with the weight. Leptin and HDL-C level decreases but TG level rises significantly. Expression of PI3K, P-PI3K decreased and expression of p70S6K, P-p70S6K increased significantly. 2. Treating with Neu-P11 or Mel, all the Biochemical assay turn to recovery.Conclusions: 1. Sleep restriction caused insulin resistance. 2. Neu-P11 could improve insulin sensitivity, increase leptin level and correct glucolipid metabolic disorder. 3. After treating with Neu-P11 and Mel, the activity of PI3K increased and p70S6K decreased in the skeletal muscles tissue of rats. We conclude that Neu-P11 or Mel improves insulin sensitivity of the rats by decreasing expression and activity of p70S6K and increasing PI3K, thus improves insulin sensitivity.