| Part Ⅰ Single-Anastomosis Duodenal Jejunal Bypass Improve Glucose Metabolism by Regulating Gut Microbiota and Short-Chain Fatty Acids in Goto-Kakisaki RatsBackground:In recent years,bariatric surgery has emerged as a promising treatment for type 2 diabetes.Bariatric surgery is known to cause alterations in the relative abundance and composition of gut microbiota,which may lead to alterations in the levels of Short-Chain Fatty Acids(SCFAs)that are produced during fermentation by gut microbes.However,little is known about the mechanism of improved glucose metabolism mediated by gut microbiota following bariatric surgery.Objective:The aim of our study was to explore whether changes in gut microbiota and in fecal SCFA could be detected following single-anastomosis duodenal jejunal bypass(DJB-sa)surgery,a type of bariatric surgery,and whether these alterations might be related to the improvement of glucose metabolism.Methods:We performed DJB-sa or Sham surgery on Goto-Kakisaki(GK)rats.Glucose metabolism was assessed with Fasting blood glucose(FBG),Intraperitoneal glucose tolerance test(IPGTT)and Fasting serum insulin(FSI).Stool samples were collected prior to and 8 weeks following surgery.The changes of gut microbiota were detected using 16S rRNA sequencing analysis.The SCFA changes in feces were assessed by Gas Chromatography-Mass Spectrometry(GC-MS).Moreover,intestinal tissues were collected to detect changes in G-protein-coupled receptor 41(GPR41)and GPR109A expression by Western blotting,in GPR43 expression by immunohistochemistry and immunofluorescence and in GLP-1 expression by Western blotting.Results:Our results showed that DJB-sa surgery was associated with a significant decrease in fasting blood glucose(FBG),intraperitoneal glucose tolerance test(IPGTT),and fasting serum insulin(FSI).And,DJB-sa led to a change in the composition of gut microbiota including an increase in the relative abundance of SCFA-producing bacteria(Bifidobacterium and Subdoligranulum).Moreover,the levels of six SCFAs in feces,as well as the intestinal expression of SCFA receptors including G-protein-coupled receptor 41(GPR41),G-protein-coupled receptor 43(GPR43),and G-protein-coupled receptor 109A(GPR109A),and the expression of Glucagon-like peptide-1(GLP-1)displayed a significant increase following DJB-sa compared with the Sham group.Conclusions:we inferred that the increase in SCFAs after DJB-sa might play a positive role to improve the glucose metabolism in association with the activation of the SCFA receptor(GPR41,GPR43 and GPR109A)/GLP-1 signaling pathway.Part Ⅱ Single-Anastomosis Duodenal Jejunal Bypass Improve Glucose Metabolism by Modulating Glucagon-like peptide-1 and Glucagon-like peptide-1 Receptor in Peripheral Organs of Goto-Kakisaki RatsBackground:DJB-sa,a type of bariatric surgery,can improve glucose metabolism and insulin sensitivity in type 2 diabetes.GLP-1 and GLP-1R have an essential function in the regulation glucose metabolism.Objective:To explore whether the DJB-sa procedure can improve glucose metabolism by modulating the expression of GLP-1 and GLP-1R in peripheral organs(intestine,pancreas,and liver).Methods:the protein expression of GLP-1 and GLP-1 R and the concentration of cyclic adenosine monophosphate(cAMP)in the intestine,pancreas,and liver was determined by immunohistochemistry(IHC),immunofluorescence(IF)and WB.Results:In GK rats,the L cells were localized next to LGR5-positive intestinal stem cells,and GLP-1 R was expressed in the liver.And,the expression of GLP-1 after DJB-sa varied among different segments of the intestine and pancreatic islet increased in size after DJB-sa.Moreover,DJB-sa enhanced the expression of GLP-1 and GLP-1 R and the level of cAMP in the intestine,pancreas,and liver.Conclusions:DJB-sa upregulated the expression of GLP-1 in the intestinal segment near the anastomotic stoma and in the distal small intestine,as well as the expression of GLP-1 R in the pancreas and the liver. |
PDF Full Text Request