The Fuction Changes Of HPA Axis And Relation With Glucose Metabolism In Four Types Of Diabetic Rat Models, And The Effect Of Rehmannia Glutinosa Oligosacchrides On HPA Axis

Objective:1. To study the fuction changes of HPA axis in four types of diabetic rat models induced by high lipid food plus stress, high lipid food plus DEX, high lipid food plus low dose STZ and alloxan (ALX), respectively, and the relation with glucose and lipid metabolism.2. To study the regulatory effect of Rehmannia glutinosa oligosaccharides (ROS) on HPA axis and related hypoglycaemic mechanism of ROS in diabetic rats.Methods:1. Four types of diabetic rat models were induced respectively:the glucose tolerant impaired rat model was induced by both high lipid food and stress (restraint with absorbent gauze, frisket, swimming in low temperature water, illumination all night and hang tail), the insulin resistance rat model was induced by both high lipid food and dexamethasone (1 mg·kg-1 bw, i.p. every other day), Type 2 diabetic rat model was induced by intraperitoneally injection of STZ (30 mg·kg-1 bw) after fed with high lipid food for two months, the diabetic rats were induced by ALX (125 mg·kg-1 bw, i.p.). Animals were divided into four groups:normal group, diabetic model group, treatment group (ROS 200 mg·kg-1·d-1, i.g.), and positive control group.2. Rat body weight and plasma glucose were evaluated every week. Rats fasted for 6 hours were decapitated after they had been administered i.g. for 4 or 5 weeks and 24-hour urine was collected in plastic tubes and immediately centrifuged at 4000 rpm for 10 min at 4℃to remove contaminants from debris of food and feces. Then total urine volume was determined and urine was kept frozen at-20℃until further analysis. Trunk blood was collected in plastic tubes containing 10 mg disodium EDTA. Whole blood was centrifuged for 5 min at 4000 rpm to separate plasma. All tissues and plasma were stored at-20℃until assay.3. Plasma glucose, lipids, CRH, ACTH, corticosterone, contents of the hepatic glycogen, skeletal muscle glycogen, hypothalamic CRH, ACTH of pituitary gland,24-hour urinary corticosterone and plasma insulin were determined. Results:1. In glucose tolerant impaired rats induced by both high lipid food and stress the concentrations of CRH, ACTH, corticosterone in plasma were higher than that's of control group and the content of ACTH in pituitary gland and corticosterone in 24-urine were increased. But plasma insulin and the content of CRH in hypothalamus were lower. Glucose and lipid metabolism were significantly ameliorated after using ROS or total saponins of Panax Ginseng for 4 weeks. The contents of ACTH in plasma and pituitary gland, and contents of corticosterone in plasma and 24-hour urine were decreased by ROS and total saponins of Panax Ginseng.2. The insulin resistance rats induced by both high lipid food and DEX the concentrations of ACTH in plasma was lower than control but plasma insulin, the contents of ACTH in pituitary gland and contents of corticosterone in plasma and 24-urine were higher compared with control group. Glucose and lipid metabolism were effectually improved after using ROS or rosiglitasone maleate for 5 weeks. The contents of contents of corticosterone in plasma and 24-hour urine were decreased by ROS treatment.3. In diabetic rat model induced by high lipid food plus low does STZ, the concentrations of ACTH, corticosterone in plasma were higher than that's of control group rats. But plasma insulin and the content of CRH in hypothalamus were low. Glucose and lipid metabolism were significantly ameliorated after using ROS or metformin for 4 weeks. The contents of ACTH in plasma and pituitary gland, and contents of corticosterone in plasma and 24-hour urine were decreased in ROS treated rats.4. In type 1 diabetic rats induced by ALX administration, the concentrations of insulin, CRH, ACTH, corticosterone in plasma were higher than that's of control group. Meanwhile the content of hypothalamic CRH, ACTH in pituitary gland and 24 h urinary corticosterone were increased. Glucose and lipid metabolism were improved after using ROS or metformin for 4 weeks. The contents of ACTH in plasma and pituitary gland and concentration of corticosterone in plasma were decreased by ROS.Conclusion:The activity of HPA axis was raised in the above diabetic rat models in our study. The function accentuation of HPA axis promotes the cortex of adrenal gland secreting too much corticosterone which inhibits insulin secretion and step up blood glucose. Therefore the disorder of glucose and lipid in those diabetic rat models may be linked to the increased activity of HPA axis and the improvement of ROS on glucose and lipid metabolism in diabetic rats may be mediated through the modulation of HPA axis activity.