| Objective:Roux-en-Y gastric bypass(RYGB)induces substantial and sustained weight loss and is a highly effective treatment for obesity-related diabetes.Duodenal-jejunal bypass(DJB)is a stomach sparing modification of RYGB.Similarly to RYGB,the DJB involves a bypass of the entire duodenum and the proximal jejunum;the stomach anatomy,however,is left unperturbed.DJB has been proven to provide significant and durable diabetes control for obesity-related diabetes.In this study,we sought to investigate gastrointestinal hormones changing in type 2 diabetes mellitus(T2DM)and the impact of T2 DM by the changes of gastrointestinal hormones and intestinal glucose metabolism after duodenal-jejunal bypass.Methods:There were 55 healthy female SPF Sprague-Dawley rats in the test.40 rats were selected as the high-fat diet(HFD)group according to a random number table and the remaining 15 rats were used as control group.The rats in high-fat diet group were fed with high-fat diet for four weeks,then injected with some streptozotocin(STZ).The control group received a chow diet.The fasting blood glucose and non-fasting blood glucose were measured after STZ injection.Glucose-dependent insulinotropic polypeptide(GIP)and glucagon-like peptide-1(GLP-1)levels were measured on 0 week,4 week and after STZ injection.34 type 2 diabetic rats were obtained,and 30 rats were divided into two groups according to a random number table: DJB group or Sham group,with 15 rats in each group.DJB and sham surgery were performed.15 age-matched normal rats were assigned as the control group.The fasting blood glucose?lipid parameters?GIP?GLP-1?glucagon and insulin levels were measured before and after surgery.Oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)was measured,and the area under blood glucose concentration curve(AUG)was calculated.Small intestine tissues were obtained 8 weeks postoperatively.RT-PCR and Western blot were used to examined gene and protein expression patterns of enzymes involved in glucose metabolism and the biosynthesis of cholesterol between the various intestinal segments of DJB-treated rats and corresponding segments of the intestine of sham-operated rats.RT-PCR wasalso used to detect Faecalibacterium prausnitzii,Bifidobacterium,Bacteroides and Lactobacillus between the various intestine contents of DJB-treated rats and corresponding segments of the intestine of sham-operated rats.Results:Fasting blood glucose and non-fasting blood glucose level were significantly higher in the HFD group compared with that in the CON group after STZ injection.Compared with CON group,the high fat diet induce a progressive decrease of GLP-1 levels and a significant increase of GIP levels and further changed after STZ injection.Compared with sham group,the fasting blood ?lipid parameters?AUGOGTT and AUGITT were significant decreased in DJB group after DJB.At the 8th week after surgery,fasting and postprandial GLP-1 level in operation group were significantly higher and postprandial GIP were significantly lower than that in sham group.Compared with fasting glucagon level,postprandial glucagon level were significant decreased in operation group.In comparison with corresponding segments of the jejunum of sham-operated rats,the small intestine of DJB-treated rats showed increased m RNA and protein levels of key enzyme involved in glucose metabolism and the biosynthesis of cholesterol,all of the discrepancies were statistically significant.A gradient in the change in gene expression levels of key factors and enzymes involved in glucose and cholesterol uptake and utilization is observed along the altered nutrient flow path in the intestine after DJB.The highest increase in m RNA levels was observed in the Roux limb and no change in RNA levels was found in the biliopancreatic limb.Lesser increase in RNA levels was observed in the proximal common limb,but no change was found in the distal comon limb.The weight of the small intestine of DJB-treated rats was three times heavier than the weight of jejunum of sham-operated rats.Body weight were not different between Sham and DJB groups.In the Roux limb and common limb,Faecalibacterium prausnitzii ? Bifidobacterium ? Bacteroides and Lactobacillus were significantly higher,all of the discrepancies were statistically significant.But no change was found in the biliopancreatic limb.Conclusion:DJB can significantly improve the glucose metabolism of T2 DM rats,the fasting blood glucose,oral glucose tolerance and insulin tolerance were significantly improved,while the weight and food intake did not change significantly.Changes in gastrointestinal hormones play an important role in the development of T2 DM.At the 8th week after surgery,changes in gastrointestinal hormones play an important role in the regulation of blood glucose homeostasis.The beneficial effect of DJB on glucose homeostasis may stem from changes in the metabolism within this reconfigured jejunal segment to meet the increased bioenergetic demands of tissue growth and maintenance,possibly in response to its exposure to undigested nutrients... |
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