Establish Model Of (Modified) Sleeve Gastrectomy And Research Its Mechanism Of Hypoglycemic By Goto-Kakizaki Rats

PartⅠEstablishment of sleeve gastrectomy in Goto-Kakizaki ratsObjective To establish sleeve gastrectomy (SG) model in the nonobese type 2 diabetic model-Goto Kakizaki (GK) rats, and to investigate that SG effects on blood glucose control.Methods Twenty three GK rats were randomly divided into the sleeve gastrectomy (SG), sham-sleeve gastrectomy (sham-SG) and pair food (PF) groups. Body weight, food intake, fasting glecmia, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and fasting plasma insulin concentration were measured in the special time of throughout the study.Results The succeeding rate of SG model is 100%. There were significant difference changes of body weight gain after the 4th operation (P< 0.01), but the fasting glycemia of SG rats was significantly improvance than PF and sham-SG groups. SG strikingly improved glucose tolerance, two weeks after surgery, the area under the blood glucose concentration curve (AUC) of SG decreased by about 28.1% compared to pre operation (P< 0.01), the AUC of SG reduced about 21% compared with PF (P< 0.01). Insulin tolerance test (ITT) and insulin resistance index (IRI) of SG rats were more significant improvement than sham-SG and PF animals.Conclusions SG is a relatively stable hypoglycemic surgical model and SG can directly controls type 2 diabetes and not secondarily to weight loss.PartⅡResearch hypoglycemic effect and mechanism of sleeve gastrectomyObjective Investigate hypoglycemic effect and its mechanism of sleeve gastrectomy (SG).Methods 30 GK rats were randomly divided into sleeve gastrectomy (SG), sham-sleeve gastrectomy (sham-SG), pair-fed (PF) and controls (Controls). Before and after surgery, we dynamically observed on changes of weight, fasting glucose, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), fasting plasma insulin, fasting plasma ghrelin and plasma GLP-1 in 24 weeks.Results From the 4th week of post-operation, the weight gain changes of SG and PF had significantly decreased compared with sham-SG and Controls group (P< 0.01). From the 2nd week post-operation, Fasting glucose concentration of SG were lower than sham-SG, PF and Controls group (P< 0.05), and the OGTT of SG rats was better improved than pre-operation and the other 3 groups. Two weeks after operation, SG was better improved glucose tolerance than pre-operation, the area under the blood glucose concentration curve (AUC) decreased by about 28.1%(P< 0.01), these effects were not seen in the sham-SG and PF animals despite similar change of weight changes and food intake. The 6th week after surgery, the results of ITT shows that insulin sensitivity of SG was obviously improvement and significantly lowered blood glucose levels compared with sham-SG group. Throughout the experiment period, we compared the hormone changes of SG and sham-SG animals, the results showed that there had no clear changes of insulin concentration (P> 0.05). Compared to sham-SG, SG significantly decreased the concentration of ghrelin (P< 0.01) and slightly raised the concentration of GLP-1 (P <0.01).Conclusions The hypoglycemic effects of SG are definite. Post-operation, SG can directly control blood glucose and not secondarily to weight loss and the decreased Ghrelin and slightly raised GLP-1 may be the major mechanism of hypoglycemic by SG.PartⅢEstablishment of modified sleeve gastrectomy in Goto-Kakizaki ratsObjective Creation and analysis of the model of modified sleeve gastrectomy by non-obese diabetic Goto-kakizaki (GK) rats.Methods 27 GK rats were randomly divided into MSG, sham-MSG, pair-fed (PF) and controls (Controls) group. Before and after operation, the changes of weight, food intake, fasting glucose, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), fasting plasma Insulin concentration, HOMA-IR and blood lipids changes were dynamically observed in 16 weeks.Results From the 4th week of post-operation, the weight gain changes of MSG had significantly decreased compared with sham-MSG and PF group (P< 0.01). Fasting glucose concentration of MSG were lower than sham-MSG, PF and Controls group, and the OGTT of MSG rats was better improved than pre-operation and the other 3 groups. Two weeks after operation, compared to pre-operation, MSG was obviously improved glucose tolerance, the area under the blood glucose concentration curve (AUC) decreased by about 38.9%(P< 0.01), these effects were not seen in the sham-MSG and PF animals despite similar weight changes and food intake. In this experiment, the insulin sensitivity and secretion of MSG were obviously improvement; these effects were not seen in the sham-MSG animals. Compared to PF and sham-MSG, the blood lipids concentration levels of MSG were significantly improvement. These results show that hindgut maybe plays a key role in the hypoglycemic effect.Conclusions MSG provides a stable, long-lasting hypoglycemic surgery model to research the mechanism of treating type 2 diabetes and is directly and effectively linked to improve the metabolism of blood glucose and blood lipids in GK rats, independently of weight loss and caloric intake.PartⅣResearch hypoglycemic effect and mechanism of modified sleeve gastrectomyObjective To study the hypoglycemic effect and its mechanism of modified sleeve gastrectomy (MSG).Methods 54 GK rats and 6 Wistar rats were randomly divided into modified sleeve gastrectomy (MSG), delayed-modified sleeve gastrectomy (D-MSG), sleeve gastrectomy (SG), sham-modified sleeve gastrectomy (sham-MSG), sham-sleeve gastrectomy (sham-SG), rosiglitazone (RSG), food restriction (FR), controls (Controls) and Wistar MSG (WMSG). Before and after surgery, each group corresponding changes were dynamically observed in 16 weeks:weight, fasting blood glucose, oral glucose tolerance (OGTT), insulin tolerance test (ITT), plasma fasting insulin, Ghrelin, GIP and plasma GLP-1. At 16th week after surgery, the gene expression of Ghrelin, GLP-1, GIP and insulin were measured in the tissues (pancreatic islets, distal ileum, duodenum and hypothalamus), and the morphological characteristics of pancreatic islets and distal ileum were investigated.Results After operation, MSG had significantly improved glucose tolerance compared with the other groups. At the 2nd week after surgery, MSG was better improved glucose tolerance than pre-operation, the area under the blood glucose concentration curve (AUC) decreased by about 38.9%(P< 0.001), the AUC of MSG reduced about 23.9% compare with SG (P= 0.007). These effects were not seen in the sham-MSG/SG and FR animals despite similar change of weight changes and less food intake. At 2nd week post-operation, D-MSG had obviously improvement compared with the pre-operation (at the 8 weeks after SG). At the 4th week after surgery, the ITT of MSG was obviously improved compared with RSG. After surgery, MSG had significantly decreased Ghrelin level (P< 0.001), increased GLP-1 level (P< 0.001) and significantly enhanced gene expression of GLP-1 and insulin gene. Immunohistochemistry examination revealed distinctly improved expression of positiveβ-cell and electron microscopy presented a remarkable increasing numbers of secretary granules in pancreatic islets of MSG, the cell edema were clear relieved. While SG and sham surgery groups had no obvious changes which were mentioned above. These results suggesting that hindgut played a key role in the hypoglycemic effect.Conclusion MSG is directly linked to the reduction in glucose levels and improvement in insulin sensitivity in GK rats, independently of weight loss and caloric intake. MSG further confirmed that the etiology of type 2 diabetes may be related to gastrointestinal hormones imbalance, re-adjust the balance of insulin endocrine axis may be an effective way to treat diabetes.