Effects Of Chronic Sleep Deprivation On Pancreatic ?-cells Function Of Rat

Epidemiological and clinical studies have shown that chronic sleep deprivation is a growing popularized phenomenon in modern society.Sleep loss is coupled with an increased risk of cardiovascular diseases,inflammatory,and neuroendocrine dysfunction,and tightly associated with metabolic syndromes.Previous studies have indicated that sleep deficiency was correlated with obesity,glucose intolerance and insulin resistance,and they were all characteristics of type 2 diabetes(T2D).The development of T2D is accompany with pancreatic ? cells dysfunction.However,the relationship between chronic sleep deprivation and islet function was poorly investigated.In the current study,we elucidated pancreatic ? cells function under conditions of restricted sleep in a rat model.We observed that chronic sleep loss decreased body weight and increased energy expenditure without changes in food intake.We examined the effects of chronic sleep disturbance on systematic metabolites in serum by using 1H NMR metabolomics and GC-FID/MS analysis.We carried out 6 metabolites(lipoproteins,triglycerides,isoleucine,valine,choline and phosphorylcholine)exhibited significantly alteration and all the fatty acids components were decreased in serum which suggested impaired fatty acid metabolism in chronic sleep disturbed rats.Meanwhile,chronic sleep loss increased blood glucose,reduced serum insulin,decreased glucose tolerance and impaired glucose-stimulated insulin secretion(GSIS)function of islets in rats.We also showed that islet dysfunction of sleep loss rats was due to reduced insulin granules docking to plasma membrane of islet.Circulating fatty acids is essential for GSIS in rat,and sleep deprivation attenuated free fatty acids in serum and impaired insulin release.We then fed sleep disturbed rats high fat diet(HFD)in order to increase the concentration of circulating fatty acids,and we found that glucose tolerance was improved and islets function was restored partly in CSD rats fed with HFD compared with CSD rats fed with normal diet.In conclusion,chronic sleep deprivation induced islets dysfunction because of decreased free fatty acids in serum.This study provides a new point of view in expounding the mechanisms of chronic sleep deprivation decreasing islet insulin secretion function,and supplying reference to healthier lifestyle.