The Study On The Relationship Between Ghrelin With Insulin Resisitance And The Observation Of The Intervention Effect On N-acetylcysteine

Objective:With the Chinese social progress and economic development, constantly improve people's standard of living, the incidence of type 2 diabetes is higher and higher. The IDF predicts that the type 2 diabetes patients reached 388 million on the global scale by 2050. In recent years, researches for the prevention and treatment of type 2 diabetes are also more and more. Especially some gastrointestinal hormones (such as secretin, somatostatin, leptin, etc) research has been paid more and more attention. One of them is named Ghrelin that is secreted by islet alpha, beta, epsilon cells and gastric mucosa cells, of which functions are in addition to increase appetite, promote feeding, increase gastric acid secretion, promote gastrointestinal motility, but also to regulate of energy balance, increase fat accumulation, meanwhile influence beta cell insulin secretion. So Ghrelin has a certain correlation with insulin resistance, and insulin resistance is the basis of type 2 diabetic. Thus the occurrence of Ghrelin and obesity, insulin resistance and type 2 diabetes have a certain correlation. In addition, oxidative stress damages pancreatic beta cells, which is one of the key factors to lesd to insulin resistance. Making use of antioxidants reduce insulin resistance and improve the function of islet, which has a profound effect on type 2 diabetes mellitus treatment. This paper which is based on induced animal model of insulin resistance by high-fat diet in rats, research on the relationship between Ghrelin and insulin resistance, and to observe the effect of N-acetylcysteine on Ghrelin and insulin resistance.Method:40 male SD rats were adaptively fed for 1 weeks, then the computer randomly divided into 2 groups: control group, namely, A group (n=10) was received normal drinking water and standard diet (70% fat and 10% protein, carbohydrate,20%); high fat group, namely, B group (n=30) was received normal drinking and high fat diet (50% fat and 30% protein, carbohydrate,20%). They were raised a total of 12 weeks. After 12 weeks, B group took the method of inner canthus to object blood, and determined fasting blood glucose and fasting insulin. Calculated insulin resistance index (HOMA-IR), to determine the establishment of 30 rats model of insulin resistance. After the successful animal model of insulin resistancem were established, the B group was divided into the high fat control group (group C, n=15) and high lipid intervention group (group D, n=15), which were continued to feed with the high fat diet, while to give A group with normal diet. Simultaneously, given the D group N-acetylcysteine 200mg/(kg�d) gavage, and A group and C group were given physiological saline by gavage for 4 weeks. After 4 weeks, the rats were put to death to collect blood, then determined fasting blood glucose by the one touch ultr, triglyceride, total cholesterol, low density lipoprotein cholesterol were determined by automatic biochemistry analyzer, and fasting insulin and Ghrelin were determined by enzyme linked immunosorbent assay (ELISA). Expression of Ghrelin in pancreas was tested by SABC immunohistochemical detection. Applicated of SPSS 13 software package statistical to analyse the data. The parameters expressed by x�s, the group data was analysed by t test analysis, and Ghrelin and relevant indicators of diabetes were analysed by Pearson correlation analysis. P<0.05 believes that there is a statistically significant difference.Result:(1)The change of each group of each index:compared with group A, the FBG, FINS, TG, CHO, LDL, HOMA IR of group C increased significantly, the difference was statistically significant (P< 0.05); compared with C group, FBG, FINS, TG, CHO, HOMA IR of group D decreased obviously, the difference was statistically significant (P<0.05); D group compared with A group had no statistical significance (P>0.05).(2)Each group the change of the serum Ghrelin level:compared with group A, Ghrelin levels of group C increased significantly, the difference was statistically significant (P< 0.05);compared with group C, Ghrelin levels of group D significantly decreased obviously, the difference was statistically significant (P< 0.05).(3)The correlation analysis of the serum levels of ghrelin and FBG, FINS, TG, CHO, LDL, HOMA IR, they presented respectively negative correlation (r value respectively 0.768,0.798,0.64,0.708,0.749,0.721, P< 0.05).(4)Each group of Ghrelin expression in the islet:compared with group A, the expression of Ghrelin rate of group C increased significantly, the difference was statistically significant (P< 0.05);compared with group C, the expression of Ghrelin rate of group D decreased obviously, the difference was statistically significant (P<0.05).Conclusion:(1)Making use of high fat diet to establish insulin resistance model, the success rate of building the model is high, and the process is simple. With the formation of animal models of insulin resistance, body weight, fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentrations present rising trend.(2) With the formation of animal models of insulin resistance, the concentration of serum Ghrelin decreased progressively, which presented respectively negative correlation with fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentration and insulin resistance index. And the expression of Ghrelin in the pancreatic tissues presented a downward trend. Therefore, it suggested that the decrease of Ghrelin secretion could be a feedback form of the body to regulate energy balance.(3) Ghrelin can inhibit the secretion of insulin. Meanwhile the levels of the serum Ghrelin secretion and pancreatic tissue Ghrelin bring down, and insulin secretion increase. It indicates that low Ghrelin levels may be independent risk factors for the development of insulin resistance and type 2 diabetes mellitus.(4)In the insulin resistance animal model, N-acetylcysteine significantly reduce fasting blood glucose, triglyceride, cholesterol, low density lipoprotein, plasma insulin concentration, increase the level of serum Ghrelin, and increase the secretion of Ghrelin in the pancreas, thus inhibiting the secretion of insulin and improving insulin resistance.