OREXIN-1-RECEPTOR BLOCKER, SB-334867 MAY AFFECT BODY WEIGHT AND PROTECT AGAINST HYPOGLYCEMIA INDUCED BY PARADOXICAL SLEEP DEPRIVATION IN ADULT MALE RATS

Abstract

Background: Sleep deprivation (SD) can affect health through its effects on many systems. Orexin is involved in regulation of many physiological functions including sleep. This can give an explanation and a way of protection against some hazards of SD. Aim: To test the protective effect of orexin-1 receptor (OX1R) blocker, SB-334867 on changes in food intake, blood glucose level and insulin sensitivity caused by SD. Method: 72 adult male rats arranged in 4 equal groups: control group, SD group, SD-OX1R blocked group & SD-DMSO group. The 3 SD groups are subjected to 8 days of paradoxical SD using the modified multiple platform method. The SD-OX1R blocked group was injected intraperitoneally daily with single dose of SB-334867 dissolved in 2 ml DMSO and diluted 1:1000 in saline (3 mg/kg/day). The SD-DMSO group was injected by DMSO alone. Food intake, body weight, blood fasting glucose & insulin levels were assessed and insulin resistance was calculated using HOMA-IR formula. Results: The SD and SD-DMSO groups showed loss of weight inspite of increased food intake plus hypoglycemia with increased insulin sensitivity. The SD-OX1R blocked group showed no significant change in food intake but more drop in body weight plus delayed changes in fasting blood glucose and insulin sensitivity. Conclusion: SD can affect health through its effect on food intake and induction of hypoglycemia. OX1R blocker, SB-334867 protects against the increase in food intake and delays increased insulin sensitivity and subsequent hypoglycemia. So, orexin most probably is a mechanism by which SD causes these changes.