AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy(SG)and duodenal-jejunal bypass(DJB).METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet(HFD)and streptozotoc...AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy(SG)and duodenal-jejunal bypass(DJB).METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet(HFD)and streptozotocin(STZ).HFD was used to induce diabetes recurrence at 4 wk postoperatively.Body weight,oral glucose tolerance test,homeostatic model assessment of insulin resistance(HOMA-IR),insulin signaling[IR,insulin receptor substrate(IRS 1,IRS2,phosphatidylinositol3-kinase and AKT in liver and skeletal muscle],oral glucose stimulated insulin secretion,beta-cell morphology(mass,apoptosis and insulin secretion),glucagon-like peptide(GLP)-1,PYY and ghrelin were compared among SG rats with common low-fat diet(SG-LFD),SG with HFD(SG-HFD),DJB rats with LFD(DJB-LFD),DJB with HFD(DJB-HFD)and shamoperation with LFD(Sham)at targeted postoperative times.RESULTS SG and DJB resulted in significant improvement in glucose tolerance,lower HOMA-IR,up-regulated hepatic and muscular insulin signaling,higher levels of oral glucose-stimulated insulin secretion,bigger betacell mass,higher immunofluorescence intensity of insulin,fewer transferase-mediated d UTP-biotin 3’nick end-labeling(TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group.The improvement in glucose tolerance was reversed at 12 wk postoperatively.Compared with the SG-LFD and DJB-LFD groups,the SG-HFD and DJB-HFD groups showed higher HOMA-IR,down-regulated hepatic and muscular insulin signaling,and more TUNEL-positive beta cells.No significant difference was detected between HFD and LFD groups for body weight,glucose-stimulated insulin secretion,betacell mass,immunofluorescence intensity of insulin,and postprandial GLP-1 and PYY levels.Fasting serum ghrelin decreased in SG groups,and there was no difference between HFD-SG and LFD-SG groups.CONCLUSION HFD reverses the improvement in glucose homeostasis after SG and DJB.Diabetes recurrence may correlate with re-impaired insulin sensitivity,but not with alterations of beta-cell function and body weight.展开更多
基金Supported by National Natural Science Foundation of China,No.81300286 to Liu SZ and No.81471019 to Hu SYFoundation for Outstanding Young Scientist in Shandong Province,No.BS2013YY031 to Liu SZ+1 种基金Science and Technology Development Program of Shandong Province,No.2014GGE27485 to Liu SZSpecialized Research Fund for the Doctoral Program of Higher Education of China,No.20130131120069 to Liu SZ
文摘AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy(SG)and duodenal-jejunal bypass(DJB).METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet(HFD)and streptozotocin(STZ).HFD was used to induce diabetes recurrence at 4 wk postoperatively.Body weight,oral glucose tolerance test,homeostatic model assessment of insulin resistance(HOMA-IR),insulin signaling[IR,insulin receptor substrate(IRS 1,IRS2,phosphatidylinositol3-kinase and AKT in liver and skeletal muscle],oral glucose stimulated insulin secretion,beta-cell morphology(mass,apoptosis and insulin secretion),glucagon-like peptide(GLP)-1,PYY and ghrelin were compared among SG rats with common low-fat diet(SG-LFD),SG with HFD(SG-HFD),DJB rats with LFD(DJB-LFD),DJB with HFD(DJB-HFD)and shamoperation with LFD(Sham)at targeted postoperative times.RESULTS SG and DJB resulted in significant improvement in glucose tolerance,lower HOMA-IR,up-regulated hepatic and muscular insulin signaling,higher levels of oral glucose-stimulated insulin secretion,bigger betacell mass,higher immunofluorescence intensity of insulin,fewer transferase-mediated d UTP-biotin 3’nick end-labeling(TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group.The improvement in glucose tolerance was reversed at 12 wk postoperatively.Compared with the SG-LFD and DJB-LFD groups,the SG-HFD and DJB-HFD groups showed higher HOMA-IR,down-regulated hepatic and muscular insulin signaling,and more TUNEL-positive beta cells.No significant difference was detected between HFD and LFD groups for body weight,glucose-stimulated insulin secretion,betacell mass,immunofluorescence intensity of insulin,and postprandial GLP-1 and PYY levels.Fasting serum ghrelin decreased in SG groups,and there was no difference between HFD-SG and LFD-SG groups.CONCLUSION HFD reverses the improvement in glucose homeostasis after SG and DJB.Diabetes recurrence may correlate with re-impaired insulin sensitivity,but not with alterations of beta-cell function and body weight.
