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. AIM To investigate factors contributing 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 among among SG rats with common low-fat diet -LFD), SG with HFD (DJ-HFD), DJB 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, h igher 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-I 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 s ensitivity, but not with alterations of beta-cell function and body weight.