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.
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.
ObjectiveTo systematically review the efficacy of Roux-en-Y gastric bypass for obesity and its comorbidities. MethodsSuch databases as PubMed, EMbase, The Cochrane Library (Issue 11, 2013), CBM, CNKI, VIP and WanFang Data, etc. were electronically searched from inception to November 2013, for including all studies on Roux-en-Y gastric bypass for obesity and its comorbidities. According to inclusion and exclusion criteria, two reviewers independently screened literature, extracted data, and evaluated methodological quality of included studies. And then meta-analysis was performed using RevMan 5.3 software. ResultsA total of 25 before and after self-control studies involving 2 966 cases with overweight or obesity were included. The results of meta-analysis showed that:after Roux-en-Y gastric bypass operation, the patients had significant reduction in BMI (MD=-16.40, 95%CI-17.42 to-15.38, P < 0.000 01), type 2 diabetes mellitus prevalence (RR=0.23, 95%CI 0.17 to 0.31, P < 0.000 01), and hypertension prevalence (RR=0.34, 95%CI 0.26 to 0.43, P < 0.000 01); besides, fasting glucose, blood pressure and serum lipid levels obviously decreased (P < 0.000 01). ConclusionRoux-en-Y gastric bypass for obesity patients is effective in reducing weight loss, type 2 diabetes mellitus incidence and cardiovascular disease incidence. Due to the limitation of the design of the included studies, the conclusion needs to be verified by further conducting high quality randomized controlled trials with large sample-size.
Objective To investigate the short term and long term effects of laparoscopic gastric bypass on obesity related type 2 diabetes. Methods Twenty obese patients with type 2 diabetes underwent laparoscopic gastric bypass between Nov. 2009 and Feb. 2012 were identified in the computer database of West China Hospital of Sichuan University. All patients had short term follow-up of less than 1 year and among them 11 were with long term follow-up of 1 year or more. Body weight， body mass index （BMI）， blood glucose， glycosylated hemoglobin （HbA1c）， homeostasis model assessment of insulin resistance-insulin resistance （HOMA-IR）， blood pressure， and blood lipids were examined. Short term （＜1 year） and long term （≥1 year） remission rates of diabetes were calculated and factors which might have effects on the remission of diabetes were analyzed. Results Of patients with short term follow-up，body weight， fasting plasma glucose （FPG）， 2h plasma glucose （2hPG）， HbA1c， and HOMA-IR were reduced significantly. Among them， 18 of 20 patients （90.0%） reached the glucose and medication standards of complete remission and partial remission， 9 patients were defined as completely remitted （9/20， 45.0%）. Those accompanied with hypertension and （or） hyperlipemia were all improved clinically. The duration of diabetes， fasting and 2 h C peptide were found to be related to short term diabetes remission. Patients with long term follow-up of 1 year or more were observed to have significant reductions in body weight， FPG， 2hPG， HbA1c， and HOMA-IR as well. Hypertension and hyperlipidemia were all well controlled. The remission rate of diabetes reached 9/11 （81.8%）and those who were defined as completely remitted took a proportion of 6/11 （54.5%）. In these patients， those who did not reach the standards of complete remission had longer duration of diabetes and higher FPG when compared with those who did. No severe adverse event was found during the follow-up in either group. Most patients investigated were satisfied with the surgery.Conclusion Laparoscopic gastric bypass is effective and safe on short term and long term treatment of obesity related type 2 diabetes.
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 observe the curative effect on non-obese type 2 diabetes and the effect on change of glucagon-like peptide-1 (GLP-1) of gastric bypass operation. Methods Thirty-two cases of gastric ulcer with non-obese type 2 diabetes were suffered gastric bypass operation. Plasma glucose concentrations, insulin and GLP-1 were measured respectively in fasting and postprandial conditions before operation and in week 1, 2, 3 and month 1, 3, 6 after gastric bypass operation, and the body mass index (BMI), homeostasis model assessment β cell function index (HBCI) and glycosylated hemoglobin (HbA1c， the index was detected only before operation and in month 3, 6 after operation) were also measured. The turnover of the diabetes condition in the 6th month after surgery was observed. Results Compared with the levels before operation, the fasting and postprandial plasma glucose levels were descending (P＜0.05), fasting and postprandial plasma insulin and GLP-1 levels were ascending (P＜0.05), HBCI was ascending and HbA1c was descending significantly after operation respectively (P＜0.05), while BMI changed un-significantly after operation (Pgt;0.05). The diabetes control rate was 78.1%(25/32) overall six months after operation. Level of GLP-1 was negatively correlated with level of plasma glucose (P＜0.05) and positively correlated with level of insulin (P＜0.05). Conclusions Gastric bypass operation can markedly reduce plasma glucose level on the type 2 diabetes patients with non-obese, and the hypoglycemic effect may be contributed by more GLP-1 secretion that caused more insulin secretion, which doesn’t depend on the loss of weight.
ObjectiveTo research the change and significance of Ghrelin and Visfatin in plasma after Roux-en-Y gastric bypass surgery (RYGB) in type-2 diabetes (T2DM) rats. MethodsThirty healthy Sprague Dawley (SD) rats (8 weeks) were divided into T2DM group (n=22) and blank control group (CSO group, n=8). Then rats of T2DM group were fed with high calorie and high sugar diet for 6 weeks, following by one dose of streptozotocin via intraperitioneal injection. Finally, there were 18 T2DM rats were successfully established. Then those 18 T2DM rats were divided into two groups:RYGB group (n=10) and sham operation group (DSO group, n=8). Rats of RYGB underwent RYGB, rats of DSO group and CSO group underwent sham operation. Levels of fasting serum glucose (FBG), fasting serum insulin (FINS), Ghrelin, and Visfatin of rats in 3 groups were detected by enzyme-linked immunoassay (EIA) before and 4 weeks after operation, and calculating the lee index and insulin sensitivity index (ISI). ResultsIn RYGB group, compared with before operation, the body weight, lee index, levels of FBG, FINS, and Visfatin decreased after 4 weeks after operation (P < 0.050), but level of ISI and Ghrelin increased (P < 0.050), while there was no significant difference in body weight, body length, lee index, ISI, levels of FBG, FINS, Ghrelin, and Visfatin in DSO and CSO group before and 4 weeks after operation (P > 0.050). In addition, there was statistical difference among the 3 groups in difference before and after operation of Ghrelin and Visfatin, the difference before and after operation of Ghrelin and Visfatin was larger than those of DSO group and CSO group (P < 0.050), but the difference was not significant differed between DSO group and CSO group (P > 0.050). ConclusionsThe increase of plasma Ghrelin and the decrease of Visfatin play important role in the mechanism after RYGB in treatment of T2DM rats.
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.
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.
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.