The Effects Of Intermittent Hypoxia On Glucose Metabolism In Rats And The Expression Of GLUT4 In Adipose Tissue And The Interventionaleffect Of Rimonabant

Objective To explore the effects of intermittent hypoxia(IH) on the glucose metabolism in rats,and on the expression of glucose transporter 4(GLUT4)and cannabinoid receptor 1(CB1R) in adipose tissue, to observe the possible mechanismof insulin resistance(IR) caused by IH, and further to investigate the interventional role of cannabinoid receptor antagonist ——rimonabant to provide a new ideas for clinical research 、prevention and treatment of OSAHS and its complications associated metabolism.Methods 32 healthy male Sprague-Dawley rats were divided into four groups according to the random number table(n = 8): normoxia control group(NC), intermittent hypoxia group(IH), intermittent hypoxia + saline group(IH + NS), intermittent hypoxia + rimonabantgroup(IH + Rim).After 4 weeks, arterial blood and tissue samples were collected.The level of fasting plasma glucose(FPG) in serum was measured by oxidase-peroxidase method,while fasting insulin(FINS) was measured with sensitive radio immunoassay.Using HOMA homeostasis model to calculate insulin resistance index(HOMA-IR) and insulin sensitivity index(HOMA-IS).Expression of CB1 R and GLUT4 in adipose tissue were determined by immunohistochemicalassay, while the expression of CB1 RmRNA ans GLUT4 mRNA in adipose tissue were detected by RT-qPCR assay.Results Firstly, compared with the NC group, the standard of FINS and HOMA-IR of rats in IH group were significantly increased, while the HOMA-IS indexwas significantly decreased, and there were no significant difference betweenthe NC group and IH + Rim group about theparameters mentioned above. Secondly, to compared with NC group, the expression level of CB1 RmRNA and the average gray scalein adipose tissue of IH group ratswere increased significantly, while the expression level of GLUT4 mRNA and the average gray scalein adipose tissuewere significantly reduced, and there were no significant difference betweenthe NC group and IH + Rim group about theparameters mentioned above. Thirdly, correlation analysis showed that the expression level of CB1 RmRNA in adipose issue was positivelycorrelated withFINS(r= 0.671) and HOMA-IR was(r= 0.643), and was negatively correlated with HOMA-IS(r=-0.569), while the expression level of GLUT4 mRNA was negatively correlated withFINS(r=-0.834) and HOMA-IR(r=-0.735), and was positivelycorrelated withHOMA-IS(r= 0.790). Fourthly, to compared with NC group, IH+Rim group with the interventional role of rimonbant showed a significantly decreased in the level of FINS、HOMA-IR, and increased level of HOMA-IS index, meanwhile, the expression level of CB1 R in adipose issue was significantly lower, the expression level of GLUT4 was increasedsignificantly.Conclusions Intermittent Hypoxia can lead to insulin resistance and endogenous cannabinoid system disorders in rats, rimonabant may partly improve insulin resistance and increase insulin sensitivity by affecting certain relevanted mechanisms of glucose transport in adipose tissue.