Melatonin And Its Analogues Improve Metabolic Syndrome In SHR Rats

Background and purpose: Metabolic dysregulation has been already more popular and has been more and more noticed by people due to the extension of night illumination and not standardly dieting, such as metabolic syndrome. Melatonin circadian rhythms may play very important role in improving people's metabolic disorder by means of receptors-mediated and receptors independent actions. We researched the role of melatonin and chemical analogues in metabolic disorder adjustment in cell level and animal level.Methods: (1) Cell experiment: Mature 3T3 - L1 adipocytes were differentiated by "cocktail" method, and were treated with 300μM oleic acid (OA) for 6 hours to establish insulin resistance cell model. Six groups of adipocytes were employed: saline control group, 10 nM Neu - p11 treatment group, 10 nM Neu - p12 treatment group, 10 nM Neu - p68 treatment group, 10 nM Neu - p150 treatment group, and 10 nM melatonin treatment group .Then we determined differences of glucose into adipocytes of all groups, using 2-[~3H]-deoxy-d-glucose uptake experiment. (2) Animal experiment: Male adult SHR aged 12 weeks are randomly divided into five groups: control SHR group (treated with 5ml vehicle through intraperitoneal injection), Neu-P11 treated SHR groups (treated with 5 mg/kg, 15 mg/kg, 50 mg/kg of Neu-P11 through intraperitoneal injection respectively) and melatonin treated SHR groups (with 10 mg/kg, through intraperitoneal injection). In addition, age-matched WKY rats are divided into five groups with the same treatments as the SHR groups to serve as control. We measured their systolic blood pressure, body weight, food intake once a week. After 5 weeks of the treatment, the blood pressure is determined by direct puncture of the carotid artery under a light ether anesthesia. and blood after fasting overnight is collected through carotid bloodletting. Finally we detect plasma Glucose,Insulin,TG,TC,HDL-C,LDL - C,Adiponectin and ANGⅡ. Result: cell experiment: The treatment groups increased respectively 756%,740%,499%,316%,508% in the counts of per minute, with Neu - p11 the best effect. Animal experiments: On one hand, melatonin can significantly lower SHR systolic blood pressure and reduce weight growth and decrease plasma Glu,ANGⅡ, Insulin, and TG. Furthermore, Melatonin can elevate Adiponectin level. On the other hand, Neu - p11 can significantly reduce the SHR weight gain and decrease plasma Glucose, systolic blood pressure, ANGⅡ, plasma Insulin, and raise plasma adiponectin level. But Neu - p11 has no influence on plasma TC, HDL-C, LDL - C, TG.Conclusion: Firstly, melatonin analogues all can promote 3T3 - L1 adipocytes to uptake glucose, and improve cell insulin sensitive, with Neu - p11 the best effect. Secondly, Neu -P11 can lower SHR systolic blood pressure, reduce body weight gain, and improve glycemia homeostasis to improve metabolic syndrome, which is accompanied with elevated plasma adiponectin and diminished ANGⅡlevels. But Neu - p11 has no influence on SHR plasma TG.