The Establishment And Appraisal Of Insulin Resistance Rats Model In Pregnant By High-Fat And High-Sugar Diet Induced And The Effect Of Dietary Intervention To This Model

BackgroundGestational diabetes mellitus (GDM) is a special type of diabetes that can bring serious harms to physical and mental health of pregnant women, fetus and newborn. GDM is found by varying degrees disorder of glucose metabolism during pregnancy for the first time. With the change in diet and the continuous improvement of living standards in recent years, the incidence rate of GDM increased year by year. Insulin resistance (IR) is considered to be the most important pathophysiological mechanisms of the incidence to abnormal glucose metabolism during in pregnancy. High-fat, high-sugar, high saturated fatty acid diet is consider to be key factors to induced GDM. Due to the limitations of the human studies, Establish the rat model of pregnancy insulin resistance is particularly important, but whether can successful induced pregnancy insulin resistance is need to be further study. Clinical studys found that only control diet and appropriate exercise to gestational diabetes, which can make impaired glucose tolerance in most of pregnancy women’ blood sugar maintained at a ideal level, but whether its mechanism of action is dependent improve insulin sensitivity was uncertain.At present the "gold standard" of measure the body peripheral tissue insulin sensitivity is the hyperinsulinemic-euglycemic clamp technology, Kraegen founded in1983, but due to technical difficulties and high spending which is rarely used in china.To solve above problems, Our experimental studys from the following aspects: First, building insulin resistance pregnancy rats models which are comply with gestational pathogenesis of insulin resistance by high-fat and high-sugar feeding, and test the model was successful established by hyperinsulinemic-euglycemic clamp technology. At the same time, mad the dietary intervention to pregnancy rats, and observed the serum markers and insulin sensitivity changes of dietary intervention’s rats which can provide reliable laboratory evidence for clinical individualized diet of pregnant women to reduce the risk of GDM.ObjectiveThe experiment test evaluation of high-fat and high-sugar diet can successful induced pregnancy rat to appear insulin resistance by the hyperinsulinemic-euglycemic clamp and observed the influence that diet intervention to the body peripheral tissue insulin sensitivity of conceive pregnancy rats which were fed with high-fat and high-sugar.Methods75SD female rats,23SD male rats, weight180g-200g, were bought at Experimental Animal Center of Zhengzhou University. Normal diet for a week for they were adapted the environment, then randomly divided the female rats into2groups:normal diet group30, high-fat and high-sugar diet group45.6weeks later, the normal diet group were divided into two subgroups:normal normal diet pregnant rat (NP) group15, normal diet virgin rat (NV) group15, and give normal diet continuing; The high-fat and high-sugar diet group were divided into three subgroups: sucrose and fat diet virgin rat (SFV) group15, sucrose and fat diet pregnant rat (SFP) group15, and dietary intervention for sucrose and fat diet pregnant rat (DIP) group15.(1) NV group:Normal female virgin rats fed by the national standard rodent diet. (2) NP group:Before and after pregnancy fed by the National standard rodent diet.(3) SFV group:Normal female virgin rats fed by high-fat and high-sugar diet.(4) SFP group:Before and after pregnancy fed by high-fat and high-sugar diet.(5) DIP group:Before pregnancy fed by high-fat and high-sugar diet, after pregnancy fed by the National standard rodent diet.Rats free feeding water. Then take the NP group, the SFP group and the DIP group male and female SD rats in the same cage pregnancy at the ratio of2:1in the seven weeks of experiment. Next morning smear female rats’vaginal secretions and observe under the microscope to see sperm (+) which be scheduled for the first day of pregnancy.18days of pregnancy, fasting but not water more than12hours, take blood at the orbital venous plexus to test the fasting insulin (Fins) and the fasting blood glucose (FBG), the total cholesterol (TC), the triglyceride (TG) and the free fatty acid (FFA).20days of pregnancy, fasting but not water more than12hours, measuring the glucose infusion rate (GIR) of the peripheral tissues of the rats by high insulin-regular euglycemic clamp experiments in each group.Analysis the measured data, compare the differences between the groups through SPSS17.0statistical software.Results(1) Compared with the SFV groups, the NP Group and the NV group, SFP rats’ body weight, cholesterol, triglycerides and free fatty acids were significantly increased, and the difference have the statistically significant (p<0.05).(2) Compared with the SFV groups, the NP Group and the NV group, SFP rats’ fasting glucose and fasting insulin were significantly increased, and the difference have the statistically significant (p<0.05).(3) At the steady-state case of the high insulin-regular euglycemic clamp experiments, compared with the SFV groups, the NP Group and the NV group, the SFP groups’glucose infusion rate (GIR)(2.9±0.7) mg·kg-1min-1were significantly reduced and the difference have the statistically significant (p<0.05). (4) Compared with the SFP groups, the weight, cholesterol, triglycerides and free fatty acids of the DIP groups rats were decreased after the dietary intervention, and the difference have the statistically significant (p<0.05).(5) Compared with the SFP groups, the fasting glucose and fasting insulin of the DIP groups rats were decreased after the dietary intervention, and the difference have the statistically significant (p<0.05). At the steady-state case of the high insulin-regular euglycemic clamp experiments, compared with the SHP groups’(2.9±0.7) mg·kg-1min-1, the DIP Groups’ GIR (8.5±0.8) mg·kg-1min-1were significantly increased, and the difference have the statistically significant (p<0.05).Conclusions(1) The pregnancy insulin resistance rats model is successful Established.(2) Dietary intervention can significantly improve the high-fat and high-sugar diet feeding pregnancy rats peripheral tissue1s insulin sensitivity.