Study On The Regulation Of Glucose Metabolism In Diabetic Rats By FXR After Duodenal Exclusion

Objective:1.We studied the effect of duodenal bypass on glucose metabolism in type 2diabetes mellitus?T2DM?model rats.The effects of duodenal reflux on glucose metabolism were analyzed.2.The changes of serum bile acid,fibroblast growth factor 15?FGF15?,and farnesoid X receptor?FXR?expressed in distal ileum after duodenal bypass in rats were analyzed to further explore the potential mechanism of metabolic bypass on treating T2DM.Methods:1.Sprague-Dawley?SD?rats were induced by high-fat diet and low-dose Streptozotocin?STZ?to be T2DM model rats.2.The model rats were randomly divided into 3 groups:sham operation group?SO,n=8?;duodenal bypass group?DB,n=8?;duodenal bypass with tube group?DBT,n=8?.3.Gastrointestinal radiography was done at 1 week after surgery.4.The food intake and weight were measured before and at 1,2,4 and 8 weeks after surgery.5.Fasting blood glucose,oral glucose tolerance test?OGTT?,bile acid,and serum FGF15 were detected before and at 4 and 8 weeks after surgery.Then the area under the curve for OGTT(AUC_OGTT)was calculated.6.During the 8th week after surgery,all rats were killed and the terminal ileums were taken to detect the level of FXR.Results:1.About 8 rats in DB group showed contrast agent refluxed into duodenum,while only 2 in DBT group showed the reflux during gastroenterography 1 week after surgery.2.There was no difference in weight and food intake between the three groups before and after operation?p>0.05?.The weight and food intake of all rats at 1 week postoperatively were significantly lower than that before surgery,and then the weight increased steadily after that.3.There was no difference in the level of fasting blood glucose in three groups before operation?p>0.05?.Postoperative DBT and DB group had lower fasting blood glucose levels than those in the sham group?SO vs.DB vs.DBT:12.9±2.5 mmol/L vs.9.8±1.7 mmol/L,9.3±1.7 mmol/L*P<0.05?.Fasting blood glucose level in DBT group was lower than that in DB group,but no statistical significance existed?p>0.05?.4.There was no significant difference in OGTT in three groups before operation?p>0.05?.OGTT and AUC_OGTT values of DBT and DB group after operation were significantly reduced than that of SO group?p<0.05?.Compared with DB group,the AUC_OGTT values of DBT group is also significantly reduced at 8 weeks postoperatively?SO vs.DB vs.DBT:2875.5±158.1 mmol/L vs.2165.3±106.4mmol/L vs.1939.3±139.3 mmol/L,*P<0.05?.5.There was no difference in serum bile acid and FGF15 levels in three groups before surgery?p>0.05?.The serum bile acid and FGF15 level of DBT and DB group were significantly higher than that of SO group?p<0.05?.?SO vs.DB vs.DBT:14.5±4.1 umol/L vs.41.2±7.0 umol/L,42.6±6.9 umol/L*P<0.05?,FGF15?SO vs.DB vs.DBT:65.5±9.3 pg/ml vs.117.2±7.6 pg/ml,126.4±11.9 pg/ml*P<0.05?.6.The expression of FXR at distal ileum of DBT and DB group at 8 weeks after operation were significantly increased than that of SO group?p<0.05?.The FXR expressions in DBT group were significantly higher than that in DB group?p<0.05?.7.The levels of serum bile acid was significantly negatively correlated with fasting blood glucose?r=-0.671,P<0.001?.Conclusion:Duodenum plays a critical role in glucose metabolism.Serum bile acid has a key role in decreasing glucose mediated by means of FXR receptor metabolism pathway.