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 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 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.
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 explore the effect of gastric bypass (GBP) on metabolic syndrome (MS) and the related mechanisms. MethodsThe literatures addressed the effect of GBP on glucose metabolism and blood pressure were retrospectively analyzed. ResultsIt showed that GBP achieved durable level of blood glucose, remission of dylipidemia and hypertension, however, which occurred before significant weight loss. The changes of many factors such as food intake, gastrointestinal hormones, adipocytokines, fat distribution might be involved in GBP to improve MS. ConclusionGBP seems to achieve the control of MS as a primary and independent effect, rather than secondary to the treatment of overweight.
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 mechanism of gastric bypass operation on treatment of type 2 diabetes mellitus, recognize the etiology and pathogenesy of the disease and frame therapy strategy for type 2 diabetes mellitus. Methods The literatures about gastric bypass operation on treatment of type 2 diabetes mellitus, including clinical cases reports and evidence-based studies were reviewed. Results Gastrointestinal bypass operation was regarded as an effective treatment for type 2 diabetes mellitus. There were three hypotheses of therapy mechanism: early delivery of nutrients to the distal intestine, exclusion of the proximal intestine and incretin/anti-incretin. Conclusion Gastrointestinal bypass operation is now considering as an effective treatment, there is still a lack of basic experimental studies to clarify the mechanism.
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 investigate the protective effect of Roux-en-Y gastric bypass surgery on early damage of renal tissue in type 2 diabetes mellitus rats, and explore the mechanism of the protective effects. MethodsDiabetes mellitus animal models were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg /kg) and a high-fat diet.Diabetic rats were divided into three groups randomly (digital table method): diabetes control group (n=8), sham operation group (n=8), and Roux-en-Y gastric bypass group (n=14).Another 8 normal SD rats as the normal control group.The fasting blood glucose, serum total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) were measured before operation and in 8 weeks after operation; plasma BUN and Cr were measured respectively before operation and in 4 and 8 weeks after operation in each group rats, 24 h urine microalbumin and urine 8-hydroxydeoxyguanosine were measured respectively before operation and in 8 weeks after operation in each group rats.Renal pathological changes were observed and the indexes of kidney hypertrophy, the mean glomerular area (MGA), and the mean glomerular volume (MGV) were analyzed in 8 weeks after operation.The expressions of fibronectin, typeⅣcollagen (CoⅣ), transforming growth factor-β1 (TGF-β1), intercellular adhesion molecule-1(ICAM-1), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), and Bcl-2 protein in renal tissues were investigated by immunohistochemical staining. ResultsRoux-en-Y gastric bypass surgery could reduce the blood glucose, blood lipid, MGA, MGV, and the index of kidney hypertrophy of diabetic rats significantly (P < 0.05), improved renal pathological morphology and kidney function (P < 0.05), reduced the protein expressions of fibronectin and CoⅣ, decreased the protein expressions of TGF-β1, ICAM-1, and NOX4, and increased the protein expression of Bcl-2. ConclusionRoux-en-Y gastric bypass surgery can improve kidney function and the pathological damage of diabetes rats, its mechanism may be related to inhibition the protein expressions of TGF-β1, ICAM-1, and NOX4, and increase the protein expression of Bcl-2.
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.