ObjectiveTo investigate the effect and mechanism of gastric bypass surgery (GBP) on fasting bloo-glucose (FBG) in type 2 diabetic rats. MethodsThe models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into two groups: diabetes-operation group (DO group, n=10) and diabetes-control group (DC group, n=10). Another twenty normal rats were randomly divided into two groups: normaloperation group (NO group, n=10) and normal-control group (NC group, n=10). The rats underwent GBP in DO group and NO group and sham operation in DC group and NC group. The FBG levels, serum dipeptidyl peptidase Ⅳ (DPPⅣ), and glucagon-like peptide-1 (GLP-1) concentrations of rats in each group were detected before operation and at 72 h, on 1 week, 4 weeks, and 8 weeks after operation. ResultsThe FBG levels of rats before operation were not significantly different between DO group and DC group or between NO group and NCgroup (Pgt;0.05). After operation, the FBG levels of rats in DO group gradually declined, reached the bottom on 4 weeks after operation and rose slightly on 8 weeks; The FBG levels of rats in DO group were lower after operation than before operation (Plt;0.05); After operation the FBG levels of rats in DO group were higher than that in NO group and NC group at the same time point (Plt;0.05); In DC group, the difference of FBG levels of rats at different time point was not statistically significant (Pgt;0.05); The inter-group and intra-group difference of FPG levels of rats for NO group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum DPP-Ⅳ of rats before operation were not significantly different in each group (Pgt;0.05). After operation, the concentrations of serum DPP-Ⅳ of rats in DO group and NO group gradually decreased and markedly lower than that before operation, respectively (Plt;0.05). The concentrations of serum DPP-Ⅳ of rats after operation in DO group and NO group were significantly lower than that at the same time point in DC group and NC group, respectively (Plt;0.05); The intragroup difference of serum DPP-Ⅳ concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum GLP-1 of rats before operation were not significantly different between DO group and DC group or between NO group and NC group (Pgt;0.05). After operation, the concentrations of serum GLP-1 of rats in DO group and NO group gradually increased, reached the top on 4 weeks after operation and declined slightly on 8 weeks; The concentrations of serum GLP-1 of rats in DO group and NO group were higher after operation than before operation (Plt;0.05);After operation, the concentrations of serum GLP-1 of rats in NO group were higher than that in NC group (Plt;0.05), but the concentrations of serum GLP-1 of rats at different time point in NO group were not different (Pgt;0.05). The intragroup difference of serum GLP-1 concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). ConclusionsThere is obvious hypoglycemic effect of GBP on FBG levels of type 2 diabetic rats other than normal rats, in which high secretion of GLP-1 and low secretion of DPP-Ⅳ may be play an important role.
Objective To study the therapeutic effect of Roux-en-Y gastric bypass （RYGB） on type 2 diabetes mellitus （T2DM） rats and explore the possible mechanism of vaspin in RYGB on T2DM. Methods Twenty SD rats with T2DM and 20 age- and sex-matched normal SD rats were randomly divided into 4 groups according to the random digits table：T2DM-RYGB group， T2DM-sham operation （SO） group，RYGB group，and SO group，10 rats in each group. Fasting plasma glucose （FPG） level，serum insulin （INS） level，vaspin level，and homeostasis model of insulin resistance （HOMA-IR） were determined before operation and on week 4，8 after operation，respectively．At the same time，the correlation between vaspin and the indicators （FPG，INS，or HOMA-IR） was analyzed．Results Compared the indicators after operation with before operation，the FPG level，INS level，vaspin level，and HOMA-IR were not significantly different between the T2DM-RYGB group and T2DM-SO group （P＞0.05） or between the RYGB group and SO group （P＞0.05），but the FPG level，INS level，vaspin level，and HOMA-IR in the T2DM-RYGB group and T2DM-SO group were significantly higher than those in the RYGB group （P＜0.05） and SO group （P＜0.05），respectively. On week 4 after operation，the FPG level，INS level，vaspin level，and HOMA-IR decreased in the T2DM-RYGB group，except for the FPG level，the other indexes had no significant differences as compared with the values before operation. On week 8 after operation，the FPG level，INS level，vaspin level，and HOMA-IR further decreased in the T2DM-RYGB group，there were significant differences of these indicators between before operation and on week 8 after operation. Compared the indicators after operation with before operation，the FPG level，INS level，vaspin level，and HOMA-IR were not statistically significant （P＞0.05） in the T2DM-SO group，RYGB group，or SO group. The changes in serum vaspin level correlated positively with those in INS and HOMA-IR before operaion and on week 4，8 after operaion in the T2DM-RYGB group and T2DM SO group rats （P＜0.05），respectively. Conclusions RYGB surgery has a therapeutic effect on T2DM rats，and serum vaspin level decreases and insulin resistance is improved after RYGB surgery，which may be one of the mechanisms of the treatment for T2DM.
Objective To summarize and analyze the research progression of zinc deficiency in patients with type 2 diabetes mellitus or obesity after Roux-en-Y gastric bypass （RYGB） surgery. Method The domestic and international published literatures about zinc deficiency after RYGB in recent years were reviewed. Results There was a degree of zinc deficiency after RYGB surgery， its mechanisms had not been fully clarified， which were related to reduced intake and absorption of zinc， protein malnutrition， dietary factors， and specific ways of surgery and the zinc supplementation programmes after operation would also affect the postoperative zinc nutritional status. Conclusions Reasons for zinc deficiency after RYGB surgery are multifaceted and have not been clarified. Further research is needed to provide experimental and theoretical basis for management of zinc nutritional status after RYGB surgery.
Objective To explore mechanism of gastric bypass in treating obesity with type 2 diabetes mellitus (T2DM) and its relationship with c-Jun N-terminal kinase (JNK) signaling pathway. Methods The INS-1 cells were divided into 4 groups according to the different treatment: control group (complete medium), high glucose group (30 mmol/L glucose medium), exendin-4 group (high glucose+100 nmol/L exendin-4), and JNK agonist group (high glucose+100 nmol/L exendin-4+JNK agonist). When these cells were cultured on day 7, the cell activity was assessed by the MTT staining. The cell apoptosis was determined by the fluorescence microscopy analysis after the Hoechst/PI staining and flow cytometric assay after the Annexin V-FITC/PI staining. The expressions of the human immunoglobulin binding protein (Bip), CCAAT/enhancer-binding protein homologous protein (CHOP), P-SAPK/JNK, and caspase-3 protein were detected by the Western blot. Results Compared with the control group, the cell activities were significantly decreased (P<0.05), the cell apoptosis rates and the P-SAPK/JNK and caspase-3 protein expression levels were significantly increased (P<0.01) in the high glucose group and the JNK agonist group, but the Bip and CHOP protein expression levels were significantly increased (P<0.01) in the high glucose group. Compared with the high glucose group, the cell activity was significantly increased (P<0.05), the cell apoptosis rate and the Bip, CHOP, P-SAPK/JNK, and caspase-3 protein expression levels were significantly decreased (P<0.01) in the exendin-4 group, the Bip and CHOP protein expression levels were significantly decreased (P<0.01) in the JNK agonist group. Compared with the exendin-4 group, the cell activity was significantly decreased (P<0.05), the cell apoptosis rate and the P-SAPK/JNK and caspase-3 protein expression levels were significantly increased (P<0.01) in the JNK agonist group. Conclusion Gastric bypass can inhibit endoplasmic reticulum stress of pancreatic islet β-cells by regulating secretion of glucagon like peptide-1, thereby inhibiting JNK signaling pathway, protecting pancreatic islet β-cells and inhibiting apoptosis, so as to achieve effect of treating T2DM.
Objective To assess the therapeutic effect of gastric bypass on type 2 diabetes mellitus (T2DM) after a one-year treatment in Mainland China. Methods Databases including The Cochrane Central Register of Controlled Trials, MEDLINE, EMbase, CBM and CNKI were searched from inception to February 2012, and the relevant journals and references of articles were also searched to collect randomized controlled trials (RCTs) or before-after self-controlled trials on gastric bypass in treating T2DM in Mainland China. Two reviewers independently screened articles according to the predefined inclusion and exclusion criteria, extracted data, and evaluated quality of the included studies. Then meta-analyses were performed using RevMan 5.1.0. Results A total of 6 before-after self-controlled trials involving 131 patients were finally included. All these trials were graded as low quality. The results of meta-analysis showed that the therapeutic effect of gastric bypass on T2DM after a one-year treatment was good. There were significant reductions in both fasting plasma glucose (1 year: SMD=–2.55, 95%CI –3.40 to –1.69, Plt;0.000 01) and glycosylated hemoglobin (1 year: SMD=–1.98, 95%CI –2.33 to –1.62, Plt;0.000 01); there was no marked change in fasting insulin (SMD=–2.03, 95%CI –4.41 to 0.35, P=0.10). Sensitivity analysis indicated that these results were stable, but funnel-plots indicated possible publication bias existed. Conclusion One year after gastric bypass, T2DM patients in Mainland China get reduced in both fasting plasma glucose and glycosylated hemoglobin, but get no improvement in fasting insulin. However, this conclusion still needs to be further proved by more high-quality and large-scale clinical trials with long-term follow-up because of the limitation of quantity, scale and quality of the included studies.
ObjectiveTo observe expre with ssions of insulin receptor substrate 1(IRS-1) and ubiquitin-protein in skeletal muscle of non-obese rats with type 2 diabetes mellitus following gastric bypass operation (GBP), and to investigate possible mechanism of GBP in improving insulin resistance. MethodsMale GK rats were randomly divided into diabetic operation group (DO group), diabetic sham operation group (DSO group), and diabetic control group (DC group), 8 rats in each group; besides 8 male Wistar rats were served as normal control group (NC group). Fasting body weight (FBW), fasting plasma glucose (FPG), and fasting insulin (FINS) were measured respectively before operation and on week 1, 2, 4 and 8 after operation. Homeostasis model-insulin resistant (HOMA-IR) index was calculated respectively before operation and on week 8 after operation. The expressions of IRS-1 protein and ubiquitin-protein in skeletal muscle were detected by using Western blot method on week 8 after operation. Results① Compared with the preoperative levels, the FBWs on week 1, 2, and 4 after operation markedly decreased (P < 0.05), but it recovered to the preoperative level on week 8 after operation (P > 0.05) in the DO group; which in the DSO group decreased on week 1 after operation (P < 0.05) and then increased on week 4 after operation (P < 0.05); which in the DC group or the NC group increased continuously and had a significant difference on week 8 after operation (P < 0.05).② The FPGs in the DO, DSO and DC groups were significantly higher than those of the NC group before operation (P < 0.05), which in the DO group decreased from (9.10±0.98) mmoL/L before operation to (5.70±0.91) mmol/L on week 8 after operation (P < 0.05) and were significantly lower than those of the DSO group or the DC group on week 2, 4, and 8 after operation (P < 0.05); which in the DC group, DSO group and NC group had no obviously changes between before and after operations (P > 0.05). ③ The FINS had no significant differences among these four groups before operation (P > 0.05), which in the DO group obviously increased[(9.64±1.59) mU/L] on week 2 after operation (P < 0.05) and then obviously decreased[(6.58±1.05) mU/L] on week 8 after operation (P < 0.05) and significantly lower than those of the DSO group or the DC group on week 8 after operation (P < 0.05), while which had no significant difference between before and after operations in the DSO group, the DC group, or the NC group (P > 0.05). ④ The HOMA-IR index in the DO, DSO or DC group was significantly higher than that of the NC group before operation (P < 0.05), which in the DO group markedly decreased from 3.18±0.50 before operation to 1.96±0.63 on week 8 after operation (P < 0.05) and significantly lower than that of the DSO group or the DC group on week 8 after operation (P < 0.05), while which had no significant difference between before and after operations in the DSO group, the DC group, or the NC group (P > 0.05). ⑤ The expression of IRS-1 protein in the DO group was significantly higher than that in the DSO group (P < 0.05) or the DC group (P < 0.05) on week 8 after operation. While there was no significant difference between the DSO and the DC group after operation (P > 0.05). ⑥ Compared with the NC group, the expression of ubiquitin-protein was significantly increased in the DO group, the DSO group, or the DC group (P < 0.05). Compared with the DSO group or the DC group, the expression of ubiquitin-protein was significantly decreased in the DO group on week 8 after operation (P < 0.05), especially it was most obvious near the molecular weight of 180×103. While there was no significant difference between the DSO group and the DC group after operation (P > 0.05). ConclusionsExpression of IRS-1 protein in skeletal muscle insulin signaling pathway in type 2 diabetes mellitus rats following GBP is increased, it might be associated with decreasing ubiquitin-protein level in skeletal muscle, thus reduces the IRS-1 ubiquitin-degradation, increase insulin sensitivity, and improve insulin resistance of skeletal muscle.
ObjectiveTo observe expressions of E3 ubiquitin ligase—mitsugmin53 (MG53) protein, MG53 mRNA, and insulin receptor substrate 1 (IRS-1) mRNA in skeletal muscle of non-obese type 2 diabetic mellitus (T2DM) rats after gastric bypass operation (GBP), and to investigate possible mechanism of GBP in improving insulin resistance.MethodsTwenty-four healthy male GK rats were randomly divided into diabetic operation group, diabetic sham operation group, and diabetic control group, 8 rats in each group; besides, 8 male Wistar rats were served as normal control group. The expressions of MG53 protein in skeletal muscle tissue were detected by using Western blot method on week8 after operation. The mRNA levels of IRS-1 and MG53 in skeletal muscles tissue were measured by RT-PCR methods on week 8 after operation.Results① The expressions of MG53 protein and MG53 mRNA in the diabetic sham operation group and diabetic control group were significantly higher than those in the diabetic operation group and the normal control group on week 8 after operation (P<0.05), respectively, which had no significant differences between the diabetic operation group and the normal control group (P>0.05), and between the diabetic sham operation group and the diabetic control group (P>0.05) on week 8 after surgery. ② Compared with the normal control group, the expression of IRS-1 mRNA was significantly decreased in the diabetic operation group, the diabetic sham operation group, and the diabetic control group (P<0.05), while there were no significant differences between the diabetic operation group, diabetic sham operation group, and the diabetic control group on week 8 after operation (P>0.05).ConclusionExpression of E3 ubiquitin ligase—MG53 protein in skeletal muscle tissue in T2DM rats following GBP is decreased, thus reduces the IRS-1 ubiquitin-degradation, increase the expression of IRS-1 protein in insulin signaling pathway of skeletal muscle tissue, and improve insulin resistance of skeletal muscle.
ObjectiveTo investigate the expressions of glucose transporter-4 (GLUT-4) and secreted protein acidic and rich in cysteine (SPARC) in adipose tissue of Goto-Kakizaki (GK)/Wister rats after gastric bypass operation (GBP), and to explore the possible mechanism of GBP improving insulin resistance.MethodsHealthy male GK rats were randomly divided into diabetic operation group (DO group, underwent GBP), diabetic sham operation group (DS group, underwent sham-operation), and diabetic control group (DC group, received no-treatment), Wister rats were set as normal control group (NC group, received no-treatment). The weight, fasting blood glucose (FPG), fasting serum insulin (Fins), and HbA1c were measured before operation and at the 1st, 2nd, 4th, and 8th week after operation. Quantitative insulin sensitivity check index (QUICKI) was measured in before operation and at the 8th week after operation, and the expressions of GLUT-4 and SPARC protein in adipose tissues were measured by Western Blot method at the 8th week after operative too.Results① Weight: the weight of the DO group was lower than preoperative at the 2nd and 4th week after GBP (P<0.05), but increased to the normal level at the 8th week after GBP (P>0.05). The weight of the DO group was lower than those of the DS group, DC group, and NC group at the same time point of 2nd, 4th, and 8th week (P<0.05). ② FPG: the FPG level of the DO group was lower than preoperative at the 2nd, 4th, and 8th week after GBP (P<0.05), and lower than those of the DS group and the DC group from 2nd to 8th week after GBP (P<0.05). The FPG level between the DS group and the DC group had no statistical significance (P>0.05). ③ Fins: the Fins level of the DO group was higher than preoperative at the 2nd week after GBP (P<0.05), and decreased gradually at 4th and 8th week but not significantly differed from the NC group at the same time point. At the 2nd week after GBP, the Fins level of the DO group was higher than those of the DS group and the DC group (P<0.05), but there was no statistical significance between the DS group and the DC group (P>0.05). ④ HbA1c: the HbA1c level of the DO group started to decrease but there was no statistical significance between preoperative and all time after GBP (P>0.05). There was no statistical significance among the 4 groups at the 8th week after GBP (P>0.05). ⑤ QUICKI: at the 8th week, the QUICKI value of the DO group was higher than preoperative (P<0.05), and at the same time, the QUICKI value of the DO group and the NC group were higher than those of the DS group and the DC group (P<0.05), but there was no statistical significance between the DO group and the NC group (P>0.05), as well as the DS group and the DC group (P>0.05). ⑥ GLUT-4 protein and SPARC protein: the expression of GLUT-4 protein of the DO group was dramatically higher than those of the DC, DS, and NC group (P<0.05), and the expression of SPARC protein of the DO group was dramatically lower than those of the DC, DS, and NC group (P<0.05) at the 8th week. But the expressions of GLUT-4 and SPARC protein had no statistical significance among the DS, DC, and NC group at the 8th week after GBP (P>0.05).ConclusionGBP may improve and increase the sensitivity of insulin resistance by regulating the expressions of GLUT-4 and SPARC protein in adipose tissue of GK rats.
Objectives To summarize the regulation of glucagon-like peptide-1（GLP-1） level by metabolism of gastrointestinal nutrients. Methods Domestic and international publications online involving regulation of GLP-1 level by metabolism of gastrointestinal nutrients in recent years were collected and reviewed. Results GLP-1 influenced insulin secretion and sensitivity， and played a leading role in recovery of glucose metabolism. Metabolism of gastrointestinal nutrients regulated GLP-1 level. Studies had shown that GLP-1 was a candidate mediator of the effects of gastric bypass （GBP） for type 2 diabetes mellitus（T2DM）. Conclusions It plays an important role in anti-T2DM effects of GBP that metabolism of gastrointestinal nutrients regulated GLP-1 level. The corresponding studies can provide a novel clinical field to treat T2DM.