| Now more than200million people suffered type2diabetes. Consequently, it is our duty to find a therapeutic method to reverse this trend. In1980s, surgery found that many patients with type2diabetes experienced a complete diabetes remission after gastric bypass surgery(GBP) for the treatment of morbid obesity. They also found the patients who had undergone gastric bypass to change the order of gastrointestinal tract experienced a better remission than the ones only underwent purely restrictive of gastirc volume operations. GBP was proved as a considerable therapy for type2diabetes by National Institute of health (NIH) and the American Diabetes Association in2008. However, the mechanism of diabetes resolution after GBP remains unclear.Glucose-dependent insulinotropic polypeptide(GIP) and glucagon-like peptide-1(GLP-1) were secreted by enteroendocrine K/L cells which located in gastrointestinal tract. GIP is mainly secreted by K cells of foregut, and the secretion of GIP is stimulated by fat of food intake. Excessive secretion of GIP will lead to harmful lipid deposition in liver, muscle and islet cells, resulting in insulin resistance and major disturbances in the secretion of insulin. The type2diabetes-related obesity will be affected by restraining the seretion of GIP; GLP-1is mainly secreted by L cells of hindgut, and be stimulated by the glucose and fat of food. Furthermore, GLP-1can promote synthesis of the glycogen and lipoclasis, inhibit gastric emptying and the scretion of glucogen, can also increase the expression of insulin gene and proliferation of β cells. Since the GBP will exclude the foregut and decrease the levels of GIP; The food intake reached hindgut rapidly to increase the levels of GLP-1after GBP, it goes without saying that GBP could play a important role in type2diabetes improving after surgery.High fat diet induces morbid obesity, the disorders of glucose and lipid metabolism. Moreover, the morbid obesity is a high risk factor for type2diabetes. As a result, our research intend to firstly give high fat diet to SD rats after GBP, and then observe the variation of glucose and lipid metabolism, as well as the effect of different concentrations high fat diet on the distribution of enteroendocrine K/L cells and the levels of GIP and GLP-1. Afterwards we will discuss the roles of GBP, the distribution of K/L cells and the levels of GIP/GLP-1played in disorders of glucose and lipid metabolism induced by high fat diet.Chapter I The effec of different concentrations high fat diet on distribution of enteroendocrine K/L cells and glucose/lipid metabolism.Objective:To discuss the change of glucose/lipid metabolism, the distribution of enteroendocrine K/L cells and the levels of GIP/GLP-1after offer the different concentrations high fat diet to SD rats.Methods:three groups of SD rats were fed by regular diet,36.3%or45%high fat diet for12weeks. The food intake,weight, the index of glucose/lipid metabolism, the distribution of K/L cells and the levels of GIP/GLP-1were be observeed.Results:The food intake and the distribution of L cells showed no difference in three groups(P>0.05). Compared with the regular diet group, the weight, fasting blood glucose, glucose tolerance, homeostasis model assessment insulin sensitivity index, homeostasis model assessment (3cell index, homeostasis model assessment insulin resistance index, triglyceride, total cholesterol, free fatty acid, the distribution of K cells and the levels of GIP/GLP-1and serum insulin was increased in the two groups of SD rats fed by high fat diet(p<0.05). Compared with36.3%high fat diet group, the distribution of K cells in duodenum and jejunum and the levels of GIP were increased in45%high fat diet group(p<0.05). The K cells mainly distributed in the duodenum and the jejunum and L cells mainly distributed in the ileum, the colon and the rectum. The distribution of K cells in the duodenum and the jejunum related to concentrations of fat in food intake(r=0.309/0.548, pearson test, p<0.05), and the distribution of L cells have nothing to do with concentrations of fat in food intake(pearson test, p>0.05), the levels of GIP related to concentrations of fat in food intake(r=0.528, pearson test, p<0.05), the levels of GLP-1have nothing to do with concentrations of fat in food intake(r=0.285, pearson test, p<0.05).Conclusions:1. High fat diet induced the disorders of glucose and lipid metabolism in SD rat.2. The K cells distributed in entire gastrointestinal, mainly distributed in the duodenum and the jejunum; L cells were not found in stomach, mainly distributed in the ileum, colon and rectum.3. The distribution of K cells and the levels of GIP that secreted by K cells was related to the concentration of fat in diet.4. The distribution of L cells and the levels of GLP-1that secreted by L cells had nothing to do with the concentration of fat in diet. Chapter Ⅱ The effec of GBP on distribution of enteroendocrine K/L cells and glucose/lipid metabolismObjective:First we want to establish the animal models of SD rat, then the change of glucose/lipid metabolism, the distribution of enteroendocrine K/L cells and the levels of GIP/GLP-1after GBP with intact gastric volume will be observed.Methods:SD rats were randomly divided in to three groups:control group, Gastric bypass(GBP) surgery group, sham operation group. The GBP was performed on GBP group:The pyloric part and the part of10cm away from distal ligament of Treitz were intersected, then side-to-side anastomosis were applied to make distal jejunum and greater curvature of stomach connection, the second side-to-side anastomotic stoma was located10cm away from the first one on the distal jejunum connecting the proximal jejunum; The sham group was performed by transections and anastomosis of the gastrointestinal tract at sites according to GBP. The complications, survival rate and liver/kidney funtion were be measured pre-and post-operations. The food intake, weight, the index of glucose/lipid metabolism, the distribution of K/L cells and the levels of GIP/GLP-1also were be measured12weeks after operations.Results:There is no complications was observed and liver/kidney funtion were showed no change between pre-and post-operations. The food intake, the index of glucose/lipid metabolism, the distribution of K/L cells and the levels of GIP/GLP-1also were showed no change during12weeks after operations, but the weight were decreased in GBP groups compare to other two groups(p<0.05).Conclusions:1. the animal models of SD rats which underwent GBP with intact gastric volume were stable and reliable.2. GBP with intact gastric volume had no effect on the distribution of K/L cells, the levels of GIP/GLP-1and glucose/lipid metabolism Chapter Ⅲ The effect of high fat diet on distribution of enteroendocrine K/L cells and glucose/lipid metabolism of SD rats which underwent GBPObjective:we want to discuss the effec of high fat diet on levels of GIP/GLP-1, distribution of enteroendocrine K/L cells and glucose/lipid metabolism of SD rats which underwent GBP.Methods:SD rats randomly divided in to two groups:regular diet group or high fat diet group, both of them were fed for12weeks. The food intake,weight, the index of glucose/lipid metabolism, the distribution of K/L cells and the levels of GIP/GLP-1were be measured during these time.Results:The food intake, fasting blood glucose, glucose tolerance, homeostasis model assessment insulin sensitivity index, homeostasis model assessment (3cell index, homeostasis model assessment insulin resistance index, triglyceride, total cholesterol, free fatty acid, the distribution of K cells and the levels of GIP and serum insulin also were showed no change during12weeks, but the weght, L cells distributed in the ileum, colon and rectum. and the levels of GLP-1were increased in high fat diet group compared to regular diet group(p<0.05).Conclusions:The exclusion of foregut, distribution of L cells and secretion of GLP-1increased may paly important roles in GBP that can improve the disorders of glucose and lipid metabolism induced by high fat diet. ChapterⅣ The role of the distribution of enteroendocrine K/L cells and GIP/GLP-1secreted by K/L cells in the disorders of glucose and lipid metabolism induced by high fat diet of SD ratObjective:we want to explore the role of the distribution of enteroendocrine K/L cells and GIP/GLP-1secreted by K/L cells in the disorders of glucose and lipid metabolism induced by high fat diet of SD ratMethods:SD rats randomly divided in to four groups:GBP group, Gastrojejunostomy(GJ) surgery group and two sham operation groups. Gastrojejunostomy surgery was performed on GJ group:the part of10cm away from distal ligament of Treitz were applied to make side-to-side anastomosis with greater curvature of stomach; The sham group was performed by transections and anastomosis of the gastrointestinal tract at sites according to GBP and GJ.Results:Compared with GJ and sham groups, the glucose tolerance, serum insulin, homeostasis model assessment insulin sensitivity index, homeostasis model assessment insulin resistance index, triglyceride, total cholesterol, and free fatty acid were better in GBP group(p<0.05), but the glucose tolerance and serum insulin in GJ groups were better than two sham groups. Fasting blood glucose and homeostasis model assessment (3cell index were showed no significance between GBP and GJ groups, but better than two sham groups. Compared with two sham groups and GJ groups, the level of GIP was decreased in GBP groups; The level of GLP-1was increased in GBP and GJ groups, there is no difference between these two groups. The distribution of L cells increased at hindgut of GBP and GJ groups, but the distribution of K cells only increased at foregut of GJ group.Conclusions:1.The secretion of GIP may be the etiological factor for the disorders of glucose and lipid metabolism induced by high fat diet, because of the distribution of K cells increasing at foregut and excessive secretion of GIP will impair the glucose metabolism finally. GIP play a important role in the disorders of glucose and lipid metabolism induced by high fat diet.2.The increase of L cells at hindgut and GLP-1secretion can improve insulin secretion and protect the function of (3cells, unless the exclusion of foregut, it can improve the disorders of glucose and lipid metabolism induced by high fat diet. GLP-1may play a important role in the disorders of glucose and lipid metabolism induced by high fat diet.
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