Changes Of Gastrointestinal Motility And Effects On GLP-1 Secretion After Sleeve Gastrectomy In Diabetic Rats

Background: Nowadays,research on obesity and Type 2 diabetes have become one of the leading and most studied topics in China and also around the world.With relatively simpler treatment methods but similar results than gastric bypass surgery,sleeve gastrectomy has been recognized by more and more doctors and patients as a new treatment for obesity and type 2 diabetes mellitus.However,the original hypothesis does not fully explain the mechanism of weight loss and glucose lowering in sleeve gastrectomy.Method: Establishment of a rat model with obesity and diabetes.And the rat model of obesity and diabetes is divided into the group of the sleeve gastrectomy group(SG group,n=10)and sham operation group(S group,n=10)randomly.Observe the change of rats' weight.OGTT test was performed to detect the blood glucose and insulin before and after operation.Through weighing of food and methylene gavage,measure gastric emptying rate and intestinal transit rate before and after operation respectively.Transition level of specific marker as c-kit mRNA and SCF mRNA in gastrointestinal pacemaker cells ICC was measured by RT-PCR.The changes of GLP-1 secretion curve between two groups after operation were measured by ELISA.The changes of L cells in two groups were detected by immunohistochemistry.Detect the transition level of GLP-1 receptor mRNA in gastrointestinal tract by RT-PCR.Results: There was no statistical significance on the weights difference between two groups before operation.The weight of SG group was significantly lower than that of sham operation group after surgery(The S group)with P?0.001.After operation,blood glucose level of SG group was significantly lower than that before operation,and the blood glucose was significantly decreased than that of S group with statistical significance.Food intake volume(g)per half hour of SG group and S group after 12 weeks were 3.70±0.25 and 4.11±0.56(P=0.049)respectively,which means feeding level of SG rats after surgery was lower than the sham operation group.The gastric emptying rate per half hour was 62.8%±9% and 52.1%±8.5%(P=0.013)respectively,which means SG rats has higher gastric emptying rate than the sham operation group post operation.Intestinal transmission: After 12 weeks,the intestinal transit rate per half hour of the SG group and the The S group was 44.5%±3.7% and + 35.9%±6.2%(P=0.001)respectively post operation,with The SG group performing higher rate.Based on results of RT-PCR:There is no statistical significance in rat transition level of c-kit mRNA,SCF m RNA from either gastric antrum or rat jejunum and ileum between the two groups.The transition level of c-kit mRNA and SCF mRNA in SG group rats was higher than S group.The secretion level of GLP-1 in SG group was significantly higher than that of S group post operation.Immunohistochemical sections' average optical density(MOD)of L cells from jejunum tissue in both groups were 0.15±0.13 and 0.13±0.15(P=0.011)respectively.The MOD of Immunohistochemical sections of L cells in ileal tissue were 0.19 ± 0.01 and 0.18 ± 0.12(P=0.005)respectively.The number of L cells in SG group from postoperative jejunum ileum and ileal tissue was significantly higher than that of S group.Conclusions:(1)Sleeve gastrectomy has a significant effect of weight loss and hypoglycemic on rats with obesity and diabetes.(2)The increase of gastric emptying rate was mainly due to decrease of gastric volume,while the increase of intestinal peristalsis rate might be related to the proliferation of ICC cells post sleeve gastrectomy.(3)Number of L cells and GLP-1R increased after sleeve gastrectomy.Intestinal peristalsis' s acceleration accelerated more undigested chime to touch L cells which further stimulated the secretion of GLP-1.Peak hour of GLP-1 postprandial secretion coincided with the moment when chyme started to meet end of jejunum and ileum anastomosis.(4)With the increase of GLP-1 secretion and earlier occur of peak hour,the peak time of insulin secretion also followed,suggesting the postprandial insulin secretion increase and blood glucose decrease were closed related to GLP-1 in SG group post operation.(5)The empty-gastric insulin secretion level of SG group post operation was lower than that of S group,and blood glucose level decreased synchronously,which suggested SG could decrease blood glucose by improvement of insulin resistance instead of increasing insulin secretion level.