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.
Objective To explore the ability of insulin-like growth factor-Ⅰ (IGF-Ⅰ) and hyaluracan acid in prompting chondrogenesis of engineering cartilage tissue.Methods Human articular chondrocytes were isolatedand cultured in DMEM plus 10% fetal bovine serum. They were divided into three groups：hyaluracan acid+chondrocytes + IGF-Ⅰ group(IGF-Ⅰ group), hyaluracan acid+chondrocytes group(cell group), hyaluracan acid group(control group). The ability of chondrogenesis was investigated by HE and toluidine blue staining, human collagen Ⅱ immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).Results Both cell group and IGF-Ⅰ group could develop into cartilage tissue in the sixth week while control group could not. The number of cartilage lacuna in IGF-Ⅰ group were more than that in cell group. Human collagen Ⅱ immunohistochemistry showed that there were ber positive cell in IGF-Ⅰ group than in cell group, collagen Ⅱ mRNA expression was more higher and collagen Ⅰ mRNA expression was lower in IGF-Ⅰ group than in cell group. Conclusion Insulin growth factorⅠ can prompt chondrogenesis of engineering cartilage tissue and ameliorate the quality of engineering cartilage tissue in vitro.
Objective To assess the tolerance of preoperative carbohydrate-rich beverage, to determine its effect on postoperative insulin resistance and analyze its potential mechanism. Methods Thirty-two patients undergoing elective colorectal cancer resection were recruited to this randomized controlled study and assigned to two groups at random. Patient in control group was fasted before operation, while patient in study group was given oral water. Homeostasis model assessment (HOMA) indexes, activity of PTK, and mRNA and (or) protein expressions of PKB, PI3K and GluT4 were measured before and (or) immediately after surgery. Furthermore preoperative well-beings of patients were studied. Results Among well-beings, feeling of thirst, hunger and anxiety tended to be better in patients receiving carbohydrate-rich beverages compared with fasted ones (P＜0.05). Whole body insulin sensitivity decreased by 33% in the study group while 38% in the control group (P=0.007 2), and the activity of PTK, expressions of PI3K and PKB in study group were higher than those in control group (P＜0.05， P＜0.01), but no significantly difference was observed about GluT4 in both groups (Pgt;0.05）. Conclusion Preoperative consumption of carbohydrate-containing fluids is safe and effective. Provision of carbohydrate energy source prior to surgery may attenuate immediate postoperative insulin resistance. A carbohydrate-rich drink enhances insulin action at the time of onset of anaesthesia or surgery by activating three kinases named PTK, PI3K, PKB which are key enzymes in pathway of insulin signal transduction. It is likely to explain the effects on postoperative insulin resistance.
Objective To investigate the expressions of insulin like growth factor binding protein -3 （ IGFBP-3 ） in serum and bronchoalveolar lavagae fluids （ BALF ） of patients with non-small cell lung cancer ， and explore the clinical significance in dignosis and prognosis of lung cancer.Methods The bronchoalveolar lavagae fluids （ BALF ） were collected by bronchoscopy in 80 cases with non-small cell lung cancer and 14 healthy subjects.The expression of IGFBP-3 in serum and BALF were detected by immunoradioassay.Results The expression of IGFBP-3 in serum and BALF of lung cancer group were significantly lower than that of health group（Plt;0.05）.IGFBP-3 levels were significantly lower in those patients with lymphoid node metastasis or metastasis or TNMⅢ-TNMⅣ than those without metastasis or TNMⅠ-TNMⅡ（Plt;0.05）.In lung cancer group，the levels of the IGFBP-3 in serum and BALF had a significantly positive correlation（r=0.415，r=0.355，Plt;0.01）.Conclusion The IGFBP-3 may play an important role in the development of non-small cell lung cancer and is valuable in dignosis and prognosis of lung cancer.
Objective To investigate the effect of combined delivery of hepatocyte growth factor (HGF) and insulinlike growth factor-1 (IGF-1) on the development of bone mesenchymal stem cells (BMSCs) differentiation by expression of GATA-4，and to supply some evidence for clinical BMSCs transplantation therapy. Methods BMSCs were isolated from the femurs and tibias of the randomly assigned rabbits and cocultured with myocytes in a ratio of 1∶1. Myocytes were obtained from neonatal rabbits ventricles. 150 ng/ml HGF and 200 ng/ml IGF-1 were added into 4 culture bottles of 8 bottles and the other 4 bottles were not. After BMSCs were cocultured with myocytes for 1 day, 3 days, 1 week, and till 6 weeks， differentiated BMSCs were targeted and microdissected with a laser capture microdissection system, and then ribonucleic acid (RNA) was extracted and isolated. The differentiation of BMSCs in coculture was confirmed by immunohistochemistry, electron microscopy, and reverse transcriptionpolymerase chain reaction (RT-PCR). And expression of GATA-4 in BMSCs was detected by semiquantitative RT-PCR. Results Before coculturing, the BMSCs were negative for α-actinin and exhibited a nucleus with many nucleoli. After coculture with myocytes, some BMSCs became αactininpositive and showed a cardiomyocytelike ultrastructure, including sarcomeres, endoplasmic reticulum, and mitochondria. BMSCs cocultured with myocytes expressed cardiac transcription factor GATA-4. IGF-1 and HGF delivery can significantly increased expression of GATA-4 for the differentiated BMSCs as compared with cells of no delivery of HGF and IGF-1. The expression level of GATA-4 in captured BMSCs began to increase at the 1st day, reach the peak at the 2nd week and kept high expression level after the 2nd week. Conclusion BMSCs can transdifferentiate into cells with a cardiac phenotype when cocultured with myocytes. Differentiated myocytes express cardiac transcription factors GATA-4. Administration of HGF and IGF-1 promoted the development of BMSCs transdifferentiate into cardiac phenotype, which is associated with the increase in expression level of GATA-4.
Objective To summarize the relationship of diabetes and its complications with microRNA. Methods Domestic and international researches were collected by searching to summarize the role of microRNA in diabetes and its complications. Results MicroRNA could affect the secretion of insulin and interfer metabolism of gulcose in fat cells， muscle cells， and liver cells， which resulting in insulin resistance. At the same time， the microRNA also played an role in damage of vascular endothelial cells and myocardial cell in diabetes. Conclusion MicroRNA acts an important role in the process of diabetes and its complications.
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 study the effect of two cytokines, basic fibroblast growth factor(bFGF) and insulin-like growth factor-I(IGF-I), on cell proliferation in chondrocytes of adult rabbits. Methods The primary chondrocytes of adult rabbits were harvested and cultured with bFGF and IGF-I at different concentrations,respectively, as well as with the mixture of the two cytokines; the quantity of cultured chondrocytes was detected by MTT assay at the 24th, 48th and 72th hours; and the final fold increase of different groups was measured by cell count for the 3rd passage; and the proliferation index of the groups was recorded by flowing cytometer on the 14th day. Results ① The cultured chondrocytes with either bFGF, IGF-I or their mixture were significantly more than that of control group at the 24th, 48th and 72th hours (P＜0.01). ② After the 3rd passage, the final folds of proliferation were significantly higher in the groups with cytokinesthan in the control group (P＜0.01); and the final fold with the mixture ofcytokines was significantly higher than that of both IGF-I and bFGF (P＜0.01). ③ Theproliferation index was significantly higher in the groups with cytokines than in the control group (P＜0.01); the proliferation index with the mixture of cytokines was significantly higher than that of both IGF-I and bFGF (P＜0.05); besides, proliferation index was higher when cytokine was applied twice than once (P＜0.05). Conclusion bFGF and IGF-I could promote chondrocytes proliferation of adult rabbits obviously and they are synergistic in cell proliferation.
Objective We investigated the effect of supplementation with alanyl-glutamine dipeptide on insulin resistance and outcome in patients with chronic obstructive pulmonary disease (COPD) and respiratory failure. Methods A prospective, randomized, open and controlled trial was conducted. Patients with COPD and respiratory failure were recruited between Jan 2005 to Feb 2006 and randomly assigned to a trial group (n=14) with glutamine dipeptide supplmented parenteral nutrition and a control group (n=16) with isocaloric, isonitrogenic parenteral nutrition. On the third day and fifth day of nutrition treatment, blood glucose was clamped at level of 4.4 to 6.1 mmol/L by intravenously bumped insulin. Blood gas, blood glucose level, insulin dosage were recorded everyday. The outcomes were mortality, length of stay (LOS) in hospital and in ICU, mechanical ventilation times and the costs of ICU and hospital.Results Thirty patients successfully completed the trial. There was no difference in blood gas between two groups, but PaO2 increased gradually. Compared with control group, blood glucose level had trend to decrease in trial group. The average insul in consumption decreased significantly in trial group on the fifth day. There was no statistical difference between two groups in mortality, length of stay in hospital and the costs of hospital. But compared with control group, length of stay in ICU and mechanical ventilation days had trend to decrease in trial group. Conclusion Alanyl-glutamine dipeptide do not improve pulmonary function of patients with COPD and respiratory failure. However, alanyl-glutamine dipeptide attenuated insul in resistance and stabilized blood glucose. This trial does not confirm alanyl-glutamine di peptide can improve outcome in critically ill patients with COPD and respiratory failure between two groups in mortality at the end of 30 days, length of stay in hospital and the costs of hospital. But the length of stay in ICU and the duration of mechanical ventilation does decrease, but not significantly, in the trial group.
ObjectiveTo verify the expression change of insulin-like growth factor-Ⅰ (IGF-Ⅰ) protein and its mRNA before and after Roux-en-Y gastric bypass surgery (RYGB) in obese rats, and to investigate the relationship between the expression of IGF-Ⅰ and proliferation/apoptosis of adipose cells. Methods① Seventy male SD rats were raised at the SPF level circumstance and were randomly divided into control group (NC group, 10 rats) and high fat diet group (60 rats). Rats of high fat diet group were given specific high fat formula diet, rats of NC group were given particular formula diet. After 6 weeks, the body weights of the rats in high fat diet group were measured, and the 20 rats of top weight were selected. The 20 obese rats were randomly divided into 2 groups:gastric bypass (GB) group (n=10) and sham-operation group (SO group, n=10). RYGB were administered to the rats of GB group, and for rats of SO group, sham operations were performed. Rats of NC group did not receive any surgery. Inguinal adipose tissues[represented the subcutaneous adipose tissue (SAT)] and epididymal adipose tissues[on behalf of visceral adipose tissue (VAT)] were taken during operation in rats of GB group and SO group respectively (0.5 g), and 12 weeks after operation in all rats of three groups. The expressions of IGF-Ⅰ protein and its mRNA in adipose tissue were detected by Western blot and real-time fluorescence quantitative PCR. ② Transfection experiment. SAT cells were divided into blank control group (BC group, without transfection), IGF-Ⅰ(+) group (gene overexpression group), IGF-Ⅰ(+) empty vector group, IGF-Ⅰ(-) group (gene silencing group), and IGF-Ⅰ(-) empty vector group. Cells were transfected with corresponding vectors with 3 duplicated holes of each group. Cell viability and apoptosis assays were carried out in 48 hours after transfection. Expressions of protein kinase B (AKT), phosphorylated protein kinase B (p-AKT), phosphoinositide 3-kinase (PI3K), and phosphorylated phosphoinositide 3-kinase (p-PI3K) were detected by Western blot meanwhile. ③ Wortmannin experiment. SAT cells were divided into Wortmannin (+) IGF-Ⅰ(+) group, Wortmannin (+) IGF-Ⅰ(-) group, Wortmannin (-) IGF-Ⅰ(+) group, and Wortmannin (-) IGF-Ⅰ(-) group, which were transfected with corresponding vectors for 24 hours, then adding Wortmannin (0.1 mmol/L). After 24 hours, the expression levels of AKT, p-AKT, p-PI3K, PI3K, and GAPDH were detected by Western blot. Results① PCR results showed that, in SAT, compared with preoperative GB group, the expression levels of IGF-Ⅰ mRNA and its protein in postoperative GB group were both lower (P < 0.01). However, the expression levels of IGF-Ⅰ mRNA and its protein between preoperative SO group and postoperative SO group showed no significant difference (P > 0.05). In VAT, the expression levels of IGF-Ⅰ mRNA and its protein in 5 groups showed no significant difference (P > 0.05). ② The MTT results showed that, IGF-Ⅰ(+) group harbored stronger proliferation abilities compared with its negative control group (P=0.04), whereas IGF-Ⅰ(-) group had lower abilities compared with its negative control group (P=0.04). The results of flow cytometry assay showed that, the apoptosis rate of IGF-Ⅰ(+) group was lower (P=0.04) than that of the corresponding negative control group, and it was higher in IGF-Ⅰ(-) group than that of the corresponding negative control group (P=0.04). ③ Compared with IGF-Ⅰ(+) empty vector group, p-PI3K/PI3K ratio (P=0.03) and p-AKT/AKT (P=0.04) ratio of IGF-Ⅰ(+) group were increased; compared with IGF-Ⅰ(-) empty vector group, p-PI3K/PI3K ratio (P=0.04) and p-AKT/AKT ratio (P=0.04) of IGF-Ⅰ(-) group were decreased. The p-AKT/AKT ratio of Wortmannin (-) IGF-Ⅰ(+) group was higher (P < 0.05) than that of Wortmannin (+) IGF-Ⅰ(+) group; the p-AKT/AKT ratio of Wortmannin (-) IGF-Ⅰ(-) group was lower than that of Wortmannin (-) IGF-Ⅰ(+) group (P < 0.05). ConclusionsIGF-Ⅰ is involved in the accumulation of subcutaneous fat in rats. RYGB can significantly reduce the expression levels of IGF-Ⅰ mRNA and its protein in subcutaneous fat of rats, so as to achieve the effect of weight loss.