Effect Of Dhea On Glucose Metabolism In Rats With Diets Of Different Energy Levels And Its Mechansim

Dehydroepiandrosterone(DHEA)is synthesized primarily by the zona reticularis of adrenal cortex and to a lesser degree by the gonads(testicle and ovary).The conjugate sulfate(DHEAS)is the main form in the circulating blood..Plenty of studies show that DHEA has an active affect on inhibiting fat deposition,improving immunity capability and antioxidation,while the mechanism is not clear yet.Our laboratory previously showed that DHEA can inhibite fat deposition in poultries and rats.As we all know,glucose metabolism has close relation to fat metabolism,but there is few report about the effect of DHEA on glucose metabolism.Therefore,this study aims to explore effects of dehydroepiandrosterone(DHEA)on glucose metabolism of rats fed different energy level diet,to provide theoretical basis and experimental evidence for application of animal husbandry production and human medicine.1.Effects of dehydroepiandrosterone(DHEA)on glycometabolism and the biochemistry mechanisms in rats fed normal diet60 male Sprague-Dawley(SD)rats were randomized into four groups,and the rats in each groups was administrated with 0 mg/kg BW,25 mg/kg BW,50 mg/kg BW and 100 mg/kg BW DHEA for 8 weeks.The results showed that 50 mg/kg BW DHEA significantly decreased body weight gain,average daily gain(P<0.05)and significantly increased ratio of feed to gain(P<0.05)when compared to the control group.50 and 100 mg/kg BW DHEA significantly increased the hepatic glycogen and muscle glycogen content(P<0.05),and 50 mg/kg BW DHEA significantly decreased the blood sugar contents(P<0.05)when compare to the control group.6-phosphofructokinase-2 and malate dehydrogenase activities were markedly increased in 100 mg/kg BW DHEA treatment group(P<0.05)than that in the control group.Pyruvate kinase and succinate dehydrogenase activities were significantly increased in 50 mg/kg BW DHEA treatment group(P<0.05).Compared to the control group,the pyruvate dehydrogenase complex El,pyruvate kinase and malate dehydrogenase activities were markedly increased in 25 mg/kg BW DHEA treatment group(P<0.05).Insulin receptor(INSR)mRNA level was markedly increased in 25 and 100 mg/kg BW DHEA treatment group(P<0.05)than that in the control group.Compared to the control group,the insulin receptor substrate-1 mRNA level was dramatically increased in 25 and 50 mg/kg BW DHEA treatment group(P<0.05),while the insulin receptor substrate-2 mRNA level was markedly increased in 50 and 100 mg/kg BW DHEA treatment group(P<0.05).In addition,glucose transporter-4 mRNA level was significantly increased in 50 mg/kg BW DHEA treatment group(P<0.05),and the glucose transporter-2 mRNA level was significantly increased in 100 mg/kg BW DHEA treatment group(P<0.05).in conclusion,our results indicated that DHEA regulated the blood glucose level via promoting glucose transportation and regulating the activates of key enzyme which involved to glycometabolism,and this actions of DHEA might be associated with its regulating the insulin receptor and insulin receptor substrate mRNA expression.2.Effect of dehydroepiandrosterone on glucose catabolism via activation of the PI3K/Akt-PFK-2 signaling pathway in rats fed a high-fat dietSeventy-five rats were randomly divided into five groups:one group was fed a normal diet(NCG)and the other a high-fat diet containing either 0(HCG),25(HLG),50(HMG),or 100(HHG)· mg kg-1 DHEA via gavage once a day for eight weeks.Long-term administration of DHEA prevented body weight gain.No statistical differences occurred in serum glucose levels,whereas hepatic glycogen content in HMG and HHG,and muscle glycogen content in HLG and HMG were higher than in HCG(P<0.01).Glucokinase,malate dehydrogenase,and phosphofructokinase-2 activities in HMG and HHG,and pyruvate kinase and succinate dehydrogenase activities in HMG were increased compared with HCG(P<0.05).Compared to HCG group,administration of DHEA increased pyruvate dehydrogenase activity(P<0.05).The phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels decreased in HMG and HHG,whereas glycogen synthase-2 mRNA levels increased in HMG compared with HCG(P<0.05).The mRNA abundance of GLUT-2 in HMG and HHG,and GLUT-4 in HMG was higher than in HCG(P<0.01).DHEA treatment increased serum leptin content in HMG and HHG compared with HCG(P<0.01).No statistical differences were observed for serum glucagon content,whereas serum insulin content and insulin receptor mRNA levels in HMG were increased in comparison with HCG(P<0.05).Insulin receptor substrate-2 mRNA levels in HMG and HHG increased compared to HCG(P<0.05).Compared to HCG,PI3K mRNA levels in HMG and Akt mRNA levels in HMG and HHG were significantly increased(P<0.05).DHEA treatment maintained normal blood glucose levels via enhancing glycogen storage and improving glucose catabolism,and this action was achieved primarily through the activation of the PI3K/Akt-PFK-2 signaling pathway.