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.
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.
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.
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 study effect of expression levels of serum inflammatory factors and insulin receptor substrate(IRS)-1/2 in visceral adipose tissue after Roux-en-Y gastric bypass(RYGB) on type 2 diabetes mellitus(T2DM) rats, and explore possible mechanism in treatment of T2DM. MethodsThe T2DM rats models were established, which were divided into 3 groups by intervention: T2MD-RYGB group(n=14), T2MD-sham operation(T2MD-SO) group(n=10), and T2MD group(n=10), and 10 normal rats were selected as control group. The rats of the T2MD-RYGB group were received the RYGB, and of the T2MD-SO group were received transection and reanastomosis of the gastroin-testinal tract. The fasting plasma glucose(FPG), fasting insulin(FINS), C-reaction protein(CRP), tumor necrosis factor-α(TNF-α), free fatty acid(FFA), homestasis model assessment for insulin resistance(HOMA-IR), adipose tissue insulin resistance(Adipo-IR) were tested respectively before operation and on week 1, 4, 8 after operation(synchronous detec-tion of rats with or without surgical intervention). The IRS-1 and IRS-2 protein contents of the rat epididymal adipose tissue were tested on week 8 after operation. ResultsThe FPG, FINS, CRP, TNF-α, FFA levels, and HOMA-IR, Adipo-IR indexes in the T2DM rats were significantly higher than those in the normal rats(P < 0.05) before operation, the above indicators on week 4, 8 after operation were significantly lower than those before operation in the T2MD-RYGB group(P < 0.05). The differences of changes among the other groups were not statistically significant(P > 0.05). The IRS-1 and IRS-2 protein expressions in the adipose tissue of the rats were significantly increased in the T2MD-RYGB group as compared with these indicators in the T2MD group and T2MD-SO group(P < 0.05), but which were significantly lower than those in the control group(P < 0.05). ConclusionsRYGB could increase IRS-1/2 expression levels in adipose tissue, which could enhance insulin sensitivity, decrease serum inflammatory factors levels, and improve insulin resistance ultimately. This might be one of the mechanisms in treatment of 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 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.
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.