| Objective:The aim of this study is to investigate the effects of chronic stress on glucose metabolism,and to further explore the role of angiotensin ? on its abnormal.Methods:In this study,male Sprague-Dawley(SD)rats were used,rats were randomly divided into four groups:1)normal control group,2)2-week restraint group,3)2-week restraint plus low dose angiotensin ? receptor-1 blocker(ARB,Candesartan)treatment group,4)2-weeks restraint plus high dose ARB treatment group.Rats were placed in the restraint chamber for 8 hours,12:00?20:00 every day.Rats were under fasting and water deprivation condition during restraint period.Body weight and fasting blood glucose level were monitored during the whole experiment period.After 14 days,glucose tolerance test was carried out,and rats were sacrificed.The liver,gastrocnemius,quadriceps and soleus were sampled.The concentration of glucokinase(GK),glucose-6-phosphatase(G-6-P),glycogen synthase(GS),insulin receptor(ISR),glucocorticoid receptor(GR)alpha and beta in liver,hexokinase(HK),lactate dehydrogenase(LDH)and succinate dehydrogenase(SDH)in muscle,and plasma insulin were measured by ELISA.Glucose transporter 2(GLUT2)mRNA was quantified in liver by PCR.Results:The results of body weight showed that the increase of body weight in stress group was significantly slower than that in normal control group,and the increase of body weight in low dose ARB treatment group was between the control group and stress group,while the increase of body weight in high dose ARB treatment group was significantly lower than that of stress group.Fasting blood glucose levels in stress group at 14 days was markedly lower than that of control group;compared with stress group,high dose ARB treatment increased fasting blood glucose level.There was no significant difference of plasma insulin levels in all groups.Data of glucose tolerance showed that increase of blood glucose concentration was higher in stress group from 15 to 60 min compared with control group,and high dose ARB treatment apparent reduced increase of blood glucose concentration at 15 min compared with stress group.ELISA results showed that liver ISR and G-6-P levels in the stress group were markedly lower compared with the control group;however,liver GS and GR-beta levels in stress group was significantly higher than that in control group,meanwhile,mRNA expression of GLUT2 in liver was lower in stress group compared with control group.High dose ARB treatment could suppress stress-induced increase of GR-beta in liver and increase stress-induced decrease of GLUT2 mRNA expression in liver.Finally,we found that ARB treatment could decrease liver LDH level.Conclusion:1.Chronic stress induces glucose metabolism abnormal in some degree,showed glucose tolerance test disorder with short time period,which might be related with the decrease of liver ISR,G-6-P,and GLUT2 expressions induced by chronic stress.2 Angiotensin ? plays an important role in chronic stress-induced changes of GR-beta and GLUT2. |
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