Background: Sleep deprivation (SD) is a growing hazard in our society in the last years which represents a major health issue that can affect health through its effects on cardiovascular system, blood glucose level and endocrine system. Orexin, a recently discovered hypothalamic neurotransmitter, is involved in regulation of many physiological functions especially sleep and food intake. Work on orexin receptors may give an explanation and a way of protection against some hazardous effects of SD.
Aim: To test the efficacy of orexin-1 receptor (OX1R) blocker, SB-334867 as a protective agent against changes in food intake, blood glucose level and insulin sensitivity caused by lack of sleep.
Method: 72 adult male rats arranged in 4 equal groups: control group, sleep deprived group, sleep deprived OX1R blocked group & sleep deprived DMSO group. The 3 sleep deprived groups are subjected to 8 days of paradoxical SD using the modified multiple platform method. The OX1R blocked group was injected daily with single dose of SB-334867 dissolved in 2 ml of DMSO and diluted 1:1000 in saline in a dose of 3 mg/kg/day for 8 successive days by intraperitoneal (i.p.) injection. The DMSO group was injected by 2 ml of DMSO alone diluted 1:1000 in saline i.p. for 8 successive days. Food intake, body weight, blood levels of fasting glucose & insulin were assessed and insulin resistance was calculated using HOMA-IR formula.
Results: The sleep deprived group and the DMSO group showed loss of their body weight inspite of increased the amount of food intake in addition to a drop in fasting blood glucose level with increase in insulin sensitivity when compared with the control group. The OX1R blocked group showed no significant change in food intake when compared with control group but more loss of weight than the other sleep deprived groups. Their fasting blood glucose showed delayed drop and delayed increase in insulin sensitivity.
Conclusion: SD can affect health through its effect on body weight and through induction of hypoglycemia and OX1R blocker, SB-334867 protects against the increase in food intake and delays the development of insulin sensitivity and subsequent hypoglycemia. So, orexin most probably is a mechanism by which SD affects body weight and blood glucose level. It is recommended to use OR1R blockers in night shift workers as a protective agent against hazardous effects of SD after further investigations to test if they have any side effects or not on other body parameters.