| 1The changes of glucose metabolism, gastrointestinal hormones and endocrine cells in the type2diabetes modeling processObjective:In this part, we studied the trends of glucose metabolism indicators and the main gastrointestinal hormones changing in the process of type2diabetes modeling. We also concerned on the changes of the intestinal endocrine cells, especially the K cells and L cells during the process, and researched the relationship between the above changes and insulin resistance.Methods:Forty male Wistar rats aged8-10weeks were randomly divided into2groups. The rats in Group1were fed with both high-sugar and high fat diet, then injected with streptozotocin (STZ), for making type2diabetes model, and were considered model group. The rats in group2also were injected with streptozotocin (STZ), but only fed with chow diet before that. The glucose metabolism index (including body weight, fasting glucose, random blood glucose, insulin, GHbA1c, OGTT) and the changes of gastrointestinal hormones (including Ghrelin, GIP, GLP-1) were observed. The KI67-positive cells, PDX-1positive cells, GIP-positive cells and GLP-1positive cells were analysed by immune-fluorescence method.Results:In the model group,14rates were successfully mad to type2diabetes model. Compared with chow diet, the glucose metabolism indexs in the model group gradually increased during the process of being fed with the high fat and sugar diet, and further increased after STZ injection, to a high and stable level. The high fat and sugar diet also induce a progressive increase of ghrelin and GIP levels, and a signi ficant decrease of GLP-1level. In the model group, the Positive rate of cells expressing KI67was53.8±8.9%. Cellular agglomerates of KI67positive cells were found inside the duodenal mucosa and muscularis mucosa, while the positive rate in the chow group is0.7±0.9%. In the model group, the Positive rate of cells expressing PDX-lwas53.8±8.9%, and cells clustered into clumps. While, the positive rate in the chow group was 29.6±9.8%, and cells were dispersed. The GIP positive cells of model group were598.2±49.6/mm3, the cells clumped together; the GIP positive cells of the experimental group were92.5±10.3/mm3, and the cells scattered in the villus epithelial.Conclusion:The high fat and sugar diet and STZ can successfully induce to type2diabetes model, in Wistar rats. The high fat and sugar diet lead to insulin resistance, and The STZ causes islet β cell function defects. The glucose metabolism indexes in the model group gradually increase during the process of being fed with the high fat and sugar diet, and further increase after STZ injection, to a high and stable level. The increase of PDX-1expression can regulate Kcell hyperplasia and lead GIP increase. This led to insulin resistance during the modeling process. The L cell proliferation significantly reduces, but the secretion of GLP-1decreases during the modeling process. The L-cell dysfunction is performanced by elevating L-cell proliferation rate. There are totally7figures,5tables and30references. 2The effects of duodenal-jejunal bypass on glucose metabolism and lipid metabolism for Type2Diabetes MellitusObjective:We compared the treatment effects of duodenal-jejunal bypass in GK rats, type2diabetic Wistar rats, Wistar rats, including glucose, lipid metabolism, GIP and GLP-1.Methods:20GK rats,20Wistar type2diabetic rats,20Wistar rats, were divided to two parts each with randomized block method, so they were six groups totally. Groups A/B/C were underwent by duodenal-jejunal bypass, while group sham-A, sham-B, sham-C by sham surgery. The stability of DJB was assessed by observing postoperative survival, liver and kidney function. The effects of DJB were assessed on glucose metabolism by observing body weight, fasting glucose, random blood glucose, GHbA1c. The changes of triglyceride (TG), total cholesterol (TC), free fatty acid (FFA) were observed, and the secretion of GIP and GLP-1were detected.Results:The survival rates of the groups were group A90.0%, Sham-A group of100.0%, group B90.0%, Sham-A group100.0%, group B100.0%Sham-C group100.0%, with no statistically significant difference. The liver and kidney function also had no significant difference between preoperative and postoperative in all the six groups. Fasting glucose, random blood glucose and GHbAlc of group A and B decreased one month, three months after surgery (P<0.05), and there was no statistically significant difference between one month and three months after surgery in the same group (P>0.05. The insulin of both one month and three months after surgery was significantly higher than preoperative (P<0.05) in the group A (P<0.05),neither was group B (P>0.05. There was no statistically significant difference about the insulin between both one month and three months after surgery in the same group (P>0.05. The TG, TC, FFA, and GIP of postoperative there months were lower than preoperative in group A and B (P<0.05), while, there was no statistically significant difference between the groups A and B. The GLP-1of postoperative there months were higher than preoperative in group A and B (P<0.05, also no statistically significant difference between groups. Conclusion:DJB is a both safe and effective surgical treatment on type2diabetes. DJB can significantly improve glucose metabolism and lipid metabolism on type2diabetic rats. GIP decrease and GLP-1increase significantly on type2diabetic rats after DJB, which maybe one important factor for the treatment of type2diabetes. There are totally3figures,5tables and13references. 3The function of GLP-1in the treatment of type2diabetes mellitus by duodenal-jejunal bypassObjective:The "hindgut" hypothesis is an important mechanism of DJB in the treatment of type2diabetes mellitus, and GLP-1is the core of the hypothesis. In this chapter, we mainly studied the impact of type2diabetes mellitus by the changes of GLP-1after DJB and the specific mechanism for the improvement of type2diabetes mellitus by GLP-1.Methods:The impacts of glucose metabolism, insulin resistance and beta cell function by GLP-1receptor agonist liraglutide and GLP-1receptor antagonist exendin9-39were observed after DJB. The impacts of glucose metabolism and intestinal hormones by DJB combined with ileal resection operation on type2diabetes were observed. The impacts of proliferation and apoptosis of pancreatic beta cells in the two parts of the experiment in this chapter were observed. The expressions of nucleic acid of glucose transporter2(GLUT2) and glucose transporter4(GLUT4) were analysed by RT-PCR.Results:Insulin secretion and beta cell function were affected by liraglutide and exendin9-39after DJB, while no obvious effect on insulin resistance. Glucose metabolism was worse than DJB after DJB combined with ileal resection, even worse than Preoperation. Compared with DJB, GIP was not significantly different after DJB combined with ileal resection, while GLP-1was significantly lower than that of DJB. Islet hyperplasia:pancreatic hyperplasia was obvious after DJB; GLP-1receptor blocking agent could decrease pancreatic hyperplasia after DJB; GLP-1receptor agonist could increase pancreatic hyperplasia after DJB; while pancreatic atrophied obviously after DJB combined with ileal resection, indicating a poor prognosis. Beta cell apoptosis:the apoptosis of pancreatic beta cells decreased significantly after DJB; the apoptosis of beta cells increased by GLP-1receptor antagonist after DJB; the apoptosis of beta cells decreased significantly by GLP-1receptor agonist after DJB, less than DJB; while the apoptosis of beta cells increased by DJB combined with ileal resection, and even appeared cell necrosis. The expression of GLUT2mRNA from high to low in GK rats:DJB combined with GLP-1receptor agonist> after DJB> before DJB> DJB combined with GLP-1receptor antagonist> DJB combined with ileal resection. The expression of GLUT4mRNA from high to low in GK rats: before DJB> DJB combined with ileal resection> DJB combined with GLP-1receptor agonist=after DJB=DJB combined with GLP-1receptor antagonist.Conclusion:GLP-1increases after DJB, and the glucose metabolism can be better improved by adding GLP-1of after DJB. GLP-1plays a key role in the treatment of type2diabetes by DJB, and GLP-1can improve type2diabetes mellitus by improving the insulin secretion. There are totally10figures,4tables and16references. |
PDF Full Text Request