Impact of chronic REM sleep deprivation on glucose homeostasis, insulin sensitivity, oxidative stress, and histological changes in adult male Wistar rats.

Sleep deprivation (SD) is a potential risk factor for the development of various metabolic disorders, including type 2 diabetes (T2D). In humans, SD has been associated with impaired glucose metabolism. To date, the link between chronic sleep deprivation (CSD) and glucose homeostasis remains unclear. To better understand the underlying mechanisms, we investigated the impact of chronic REM-SD on glucose homeostasis, insulin sensitivity, and physiological functions in Wistar rats, as well as on markers of oxidative stress and histopathological changes observed in organs. Eighteen adult male Wistar rats were randomly divided into three groups: CSD, WP, and control (CON). Rats in the CSD group (n = 6) were subjected to daily REM sleep deprivation for 18 h/day (16:00 to 10:00) for five weeks using the modified multi-platform method (MMPM). An intraperitoneal glucose tolerance test and an insulin tolerance test were performed after REM-SD and a 12-h fasting period, respectively. The changes induced by REM-SD were assessed by monitoring body weight, water and food consumption, and the measurement of regulatory hormones such as acetylcholinesterase and corticosterone, insulin, and the HOMA-IR score. Biochemical parameters such as glucose, TG, TC, LDL, HDL, ASAT, ALAT, TP, ALB, CPK, CREA, URE, and LDH were also measured. In addition, an oxidative stress and histopathological study was performed on various organs. After REM-SD, rats exhibited glucose intolerance and also developed increased insulin sensitivity. Elevated plasma glucose levels, plasma levels of CORT, LDH, markers of oxidative stress, and decreased plasma levels of BuChE, as well as impaired hepatic and pancreatic function, confirmed by significant histopathological changes, were observed. Ticking together, these modifications and alterations in physiologic mechanisms induced by CSD lead to hyperglycemia, glucose intolerance, and insulin resistance. Our funding suggests that oxidative stress and cytotoxicity are the key potent mechanisms responsible for the impact of chronic REM-SD on the development of T2D in rats.