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Objective To investigate the expression of glucose transporters 1 (GLUT-1) in gastric cancer and its relation with clinicopathological characteristics and prognosis. Methods PubMed, Web of Science,EMbase,Cochrane Library,WanFang Databases and China National Knowledge Internet(CNKI)were used to search literatures about GLUT-1 and gastric cancer. From the day of establishment to May 15, 2017, according to the inclusion and exclusion criteria, 2 researchers independently screened studies, extracted data and assessed quality of the included studies. Effect value and 95 % CI was calculated respectively. Then Meta-analysis was conducted by using RevMan5.3 software. Results A total of 11 articles were enrolled, including 1 714 cases in the gastric cancer group and 431 cases in the normal gastric mucosa group. The results of Meta-analysis showed that GLUT-1 expression was higher in the gastric cancer group than that in the normal group, and there was a significant difference (OR= 24.23, 95 % CI 11.86-49.51, P< 0.000 01). The expression of GLUT-1 was not related with age, gender, tumor size and invasion depth (all P> 0.05), but related with differentiated degree (OR= 0.41, 95 % CI 0.25-0.67, P= 0.000 4), lymphatic metastasis (OR=5.11, 95 % CI 2.73-9.56, P<0.000 1), and TNM staging (OR= 0.32, 95 % CI 0.20-0.51, P< 0.000 01). Moreover, GLUT-1 had a correlation with the overall survival rate of gastric cancer (HR= 1.61, 95 % CI 1.30-1.99, P < 0.000 1). Conclusions GLUT-1 protein expression is higher in gastric cancer tissues than that in normal gastric mucosa, and it is related to tumor differentiation degree, lymph node metastasis, TNM staging.Besides,GLUT-1 may be correlated with poor prognosis of patients with gastric cancer.
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Objective To observe the effect of paeoniflorin on insulin resistance in rats fed with high-fat diet and to investigate the possible mechanisms.Methods Male Sprague Dawley (SD) rats were randomized into 4 groups:normal control,high-fat diet,high-dosage paeoniflorin (HDP group),and lowdosage paeoniflorin (LDP group).The control group was fed with ordinary diet,while the others with highfat diet,paeoniflorin intervention groups were given low-or high-dosage paeoniflorin by intraperitoneal injection.After 6 weeks,fasting serum triacylglycerol (TG),total cholesterol (TC),free fatty acids (FFA),fasting blood glucose (FBG),and insulin were determined.Insulin sensitivity index (ISI) were calculated and then the animals were sacrificed to acquire epididymal fat mass.The tumor necrosis factor alpha (TNFα) and glucose transporter 4 (Glut4) expressions in adipose tissue were detected by quantitative realtime polymerase chain reaction(PCR).Results Compared with high-fat fed group,HDP group had lower epididymal fat pad weight,reduced level of FBG,insulin and FFA (P ＜0.05) and improved ISI(-5.84 ± 0.24 vs-6.44 ± 0.25,P ＜ 0.05).LDP group had similar trends.In adipose tissue,the TNFα expression in LDP and HDP group was lower,Glut4 expression in HDP group was higher than that of high-fat fed group (P ＜ 0.05).Conclusion Paeoniflorin can reduce visceral adipose content,inhibit TNFα expression and increase Glut4 expression in adipose tissue,eventually lower glucose,and improve insulin resistance caused by high-fat diet.
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Objective: To observe influence of exercise on expressions of peroxisome proliferators-activated receptor-γ (PPAR-γ) and glucose transporter-4 (Glut-4) in skeletal muscle tissue of mice with insulin resistance (IR) induced by high fat diet, and preliminarily investigate mechanism of swimming training improves IR. Methods: A total of 30 eight-week-old healthy male C57BL /6J mice were randomly divided into normal diet group (n=10), high fat diet group (n=10) and high fat diet + exercise group (HE group, n=10, mice received 12-week swimming training). Body weight and fasting blood glucose (FBG) of mice were measured every week. After 12-week swimming training, fasting insulin (FINS) was measured by radioimmunoassay and IR index (IRI) was calculated; expressions of PPAR-γ and Glut-4 mRNA in skeletal muscle tissue were detected by reverse transcription polymerase chain reaction (RT-PCR). Results: Compared with normal diet group, body weight significantly increased in high fat diet group; body weight of HE group was significantly lower than that of high fat diet group (P<0.05). Compared with normal diet group, there were significant increase in FINS, FBG and IRI in high fat diet group and HE group (P<0.01). Compared with high fat diet group, there were significant decrease in FINS [(14.00±7.12) mmol/L vs. (10.17±3.88) mmol/L], FBG [(9.49±1.28) mmol/L vs. (8.03±1.67) mmol/L] and IRI [(1.47±0.38) vs. (1.06±0.27), P<0.05 all], and significant increase in expressions of PPAR-γ [(0.95±0.17) vs. (2.37±0.41)] and Glut-4 mRNA [(0.68±0.24) vs. (1.54±0.28), P<0.01 both] in HE group. Conclusions: Exercise may significantly improve insulin resistance, and the mechanism may be related with upregulation of expressions of PPAR-γ and Glut-4 mRNA in skeletal muscle, regulation of glucose metabolism and promotion of transduction of insulin signal.
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Objective To discuss the molecular mechanism of 18F-fluorodeoxyglucose (FDG) uptake in tumor and to assess its value to identify pathologic type and cancer staging in patients with earlystage nasopharyngeal carcinoma.Methods Forty patients with nasopharyngeal carcinoma of early-stage,including 12 cases with T1 stage and 28 cases with T2 stage, underwent FDG PET imaging.The maximum standardized uptake value ( SUVmax ) and mean standardized uptake value ( SUVmean ) of FDG uptake of each patient were measured and compared between T1 and T2 stage by t-test.The expression of glucose transport protein 1 ( Glut1 ) and hexokinase- Ⅱ ( HK- Ⅱ ) of each case was measured in paraffin sections by streptavidin-perosidase (SP) immunohistochemistry.The positive expression rate of Glut1 and HK- Ⅱ was calculated and compared between T1 and T2 by x2 test.Meanwhile, the correlation between the expression of Glut1 or HK-Ⅱ and the SUVmax was tested by Pearson analysis.Results The SUVmax and SUVmean in 40 patients were 9.45 ± 1.87 and 6.04 ± 1.09, respectively.The SUVmax of patients with T1 stage (8.95 ± 1.91 ) was significantly lower (t =4.46, P＜0.001 ) than that of patients with T2 stage (11.55 ± 1.70), and the SUVmean of patients with T1 stage (5.61 ± 1.08) was significantly lower ( t = 6.76, P ＜ 0.001 ) than that of patients with T2 stage (7.98 ± 1.10) too.Among 40 patients, all patients showed positive expression of Glut1 and HK-Ⅱ , and the positive expression rate of Glut1 and HK-Ⅱ was ( 45.2 ± 10.9 )% and ( 68.3 ±9.5)%, respectively.The positive expression rate of Glut1 was (38.4 ±8.1)% in T1 stage and (49.7 ±12.6)% in T2 stage, which displayed no difference (x2 =40.58, P＞0.05), but the HK-Ⅱ positive expression rate showed significant difference (x2 =58.71, P＜0.05) between T1 stage (60.1 ±11.1)% and T2 stage (77.9 ± 14.7 )%.The correlation analysis indicated that there was low-degree positive correlation (r =0.369, P=0.019) between the SUVmax and Glut1 expression, and there was medium-degree positive correlation (r = 0.549, P = 0.001 ) between the SUVmax and HK-Ⅱ expression.Conclusion Expression of Glut1 and HK-Ⅱ was positively correlated with FDG uptake in patients with early-stage nasopharyngeal carcinoma.
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Objective To investigate the effects of high glucose and insulin on the expression of glucose transporter 4 (GLUT4), Cbl-associated protein (CAP) and cytoskeleton protein F-actin of glomerular mesangial cells (GMCs), in order to explore the function of GLUT4, Cbl-associated protein and F-actin in the pathogenesis and development of diabetic nephropathy (DN). Methods Cultured 1097 rat glomerular mesangial cells were divided into 8 groups: control, 10-9 mol/L insulin, 10-8 mol/L insulin, 10-6 mol/L insulin, high glucose (30 mmol/L), mannitol (25 mmol/L mannitol+5 mmol/L glucose), high glucose plus 10-6 mol/L insulin, high glucose plus 10-9 mol/L insulin. Expression of CAP mRNA and GLUT4 was measured by RT-PCR and immunohistochemistry method. F-actin was stained by rhodamine-pholloidin and the fluorescent intensity was calculated by image analysis system. Results The expression of GLUT4 mRNA and protein, CAP mRNA was found in normal giomerular mesangial cells (control), and there was no significant difference in 10-9 mol/L insulin group. The expression of GLUT4 mRNA (P<0.05) and protein (P<0.01), CAP mRNA (P<0.01) level was decreased in high glucose group compared with that of control group, but there was no significant difference in mannitol group. The expression of GLUT4 and CAP mRNA up-regulated with the increase of concentration of insulin. The expressions of GLUT4 mRNA in 10-8 mol/L insulin and 10-6 mol/L insulin groups were 2.06-fold and 2.66-fold of 10-9 mol/L insulin group, of GLUT4 protein were 1.93-fold and 2.83-fold of control, and of CAP mRNA were 1.91-fold and 2.15-fold of control, respectively. The expressions of GLUT4 mRNA, GLUT4 protein, CAP mRNA in high glucose plus insulin group were 2.15-fold, 2.08-fold, 2.14-fold of high glucose group respectively. High glucose decreased the fluorescent intensity of F-actin to 44.5% (P<0.01). 10-8 mol/L insulin and 10-6 mol/L insulin groups increased to 1.224-fold (P<0.05), 1.296-fold (P<0.01) in a concentration-dependent manner. The spearman correlation coefficient between GLUT4 and F-actin was 0.929 (P=0.001), between GLUT4 mRNA and CAP mRNA was 0.905 (P=0.002). Conclusions (1) A certain expression of GLUT4 mRNA and protein, CAP mRNA from GMC is found in normal glomerular mesangial cells. (2) High glucose can inhibit the expression of GLUT4 and CAP mRNA significantly, and facilitate the depolymerization of F-aetin. (3) Insulin can reverse down-regnlation of GLUT4 and CAP mRNA caused by high glucose. (4) GLUT4, CAP and F-actin are important factors in the development of DN.
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Objective To investigate the biological effects of insulin resistance(IR)on the porcine granulosa cells which iS induced by wortmannin,the PI-3K inhibitor and mediated by key molecules including GLUT4 and MAPK during insulin signaling.Methods The model of IR porcine granulosa cell was established in in vitro culture by treatment of wortmannin,and was assessed the amount of3H glucose uptake as well as medium glucose levels by glucose oxidase method.The protein and mRNA expression of GLUT4 and MAPK were evaluated by immunofluorescence and RT-PCR respectively.Resuits The glucose intake was decreased by 40% with treatment of wortmannin at 1.5 μmol/L(P＜0.05).GLUT4 and MAPK were localized mainly to cytoplasm of grantdose cells.When granulosa cells were insulin resistant,the expression of GLUT4 was down-regulated whereas MAPK was up-regulated as compared with the controls.Conclusions Wortmannin treatment can lcad to decreased expression of GLUT4 and increase of IR granulose cells.This metabolic phenotype could induce increased expression of MAPK and mitogenic potential,indicating the cross-talk between two pathways of insulin signaling within ovarian cells.
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0.05),but expression of VEGF,GLUT1 and MDR1 were all enhanced and overall proliferation was promoted,apoptosis inhibited [(11.46?0.28)% vs (29.27?0.18)%,(15.77? 0.49)% vs (31.13?0.08)%],and transmembrane behavior enhanced [(37?12)% vs (26?7)%, (40?9)% vs (28?5)%],and the variations were significant (P
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Objective To study the expression of glucose transporter-1 (GLUT_1) and its correlation with basic fibroblast growth factor (bFGF) and proliferating cell nuclear antigen (PCNA) in epithelial ovarian neoplasm. Methods Streptavidin-peroxidase complex technique was used to examine the expression of GLUT_1, bFGF and PCNA protein in six cases of normal ovarian tissue, 20 cases of benign epithelial tumors, seven cases of borderline tumor and 44 cases of epithelial ovarian carcinoma. Results In normal ovary and benign ovarian tumor, GLUT_1 was not detected,but in borderline ovarian tumor and cancer, the positive expression ratio of GLUT_1 was 6/7 and 91%(40/44), respectively. The intensity of GLUT_1 in ovarian epithelial neoplasm was significantly higher than in borderline tumors. The staining intensity of GLUT_1 was significantly correlated with the histological grade of the tumor (r_S=0.499, P=0.001), and was positively correlated with the clinical stage, cancer invasion and lymph node metastasis. GLUT_1 staining was intense in cytoplasmic membrane, and was stronger in areas far away from blood vessels and near the necrotic center. GLUT_1 expression level did not show any association with histology type (P=0.513). bFGF positive rate in tumor was 57%(25/44). The staining intensity of GLUT_1 was significantly higher in bFGF positive group than in bFGF negative group (P
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Objective To explore the effect of glucose transporter(GLUT) expression in human term placenta when complicated with fetal growth restriction (FGR) and its correlation with maternal serum cortisol level. Methods Twenty pregnant women with FGR and 24 normal pregnant control were selected. The distribution of GLUT_1 in human placenta was detected by immunohistochemistry and the serum cortisol level by radioimmunoassay before delivery.The birth weight and the placental weight were measured at delivery. Results The expression of GLUT_1 in FGR group was lower than that of the control (149.8?8.2 vs 155.9?6.5, P
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AIM: To investigate the volume percentage of infarct and expression level of glucose transporter-3 (GLUT3) transcription and protein at different ischemic time points and different reperfusion time points in rat focal cerebral ischemic penumbra. METHODS: Focal ischemic models of middle cerebral artery occlusion (MCAO) in rats were made by inserting nylon thread. Brain samples were harvested from ischemic penumbra. Infarct volume was analyzed quantitatively by Kontron IBAS 2.5 image auto-analyses system. The change of GLUT3 mRNA was assessed by RT-PCR, and the expression of GLUT3 protein was assessed by immunohistochemistry. RESULTS: The infarction volume in MCAO 1 h/R group was obviously smaller than that in MCAO 3 h/R group. GLUT3 began to ascend at 3 h in MCAO 1 h/R group, reached to climax at 24 h and remained higher than normal at 1 week. In contrast, in the MCAO 3 h/R group, GLUT3 had a descent at 3 h. Later on, it ascended rapidly, and reached climax at 24 h. At 1 week, it approached to normal. The expression level of GLUT3 protein corresponds with that of mRNA. CONCLUSION: GLUT3 expression is up-regulated in the penumbra region after focal cerebral ischemia, it may be a protective reaction against ischemia/reperfusion injury. [
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AIM: To investigate the volume percentage of infarct and expression of glucose transporter-1 (GLUT1) transcription and protein levels at different ischemic time point and different reperfusion time point in rat focal cerebral ischemic penumbra. METHODS: Focal ischemic models of middle cerebral artery occlusion (MCAO) in rats were made by inserting nylon thread. Brain samples were harvested from ischemic penumbra. Infarct volume were analyzed quantitively by Kontron IBAS 2.5 image auto-analyses system. The expressien of GLUT1 mRNA was assessed by RT-PCR, and the expression of GLUT1 protein was assessed by immunohistochemistry. RESULTS: The infarction volume in MCAO 1 h/reperfusion (R) group was obviously smaller than that in MCAO 3 h/R group. GLUT1 increased at (1 h) MCAO 1 h/R group, climbed to climax at 24 h and remained higher than normal at 1 week. In contrast, in the MCAO 3 h/R group, the corresponding index was at 3 h, 24 h and 1 week, but the increasing degree of GLUT1 was slighter than MCAO 1 h/R. GLUT1 protein began to ascend at 1 h, reached climax at 24 h and was higher than normal at 1 week in MCAO 1 h/R group, while in MCAO 3 h/R group, the corresponding index was at 3 h, 24 h and 1 week. CONCLUSION: GLUT1 expression is notably up-regulated in the penumbra region after focal cerebral ischemia, it may be a protective reaction against ischemic injury. [
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Increased expression of glucose transporter1 (GLUT1) has been reported in many human cancers. We hypothesized that the degree of GLUT1 might provide a useful biological information in gastric adenocarcinoma. RT-PCR and immunostaining were used to analyze GLUT1 expression in gastric cancer. RT-PCR showed GLUT1 expression was not largely detected in normal gastric tissue but was detected in cancerous gastric tissue of counterpart. By immunohistochemistry, GLUT1 protein was absent in normal gastric epithelium and intestinal metaplasia. 11 of 65 patients with gastric adenocarcinoma had specific GLUT1 immunostaining in a plasma membrane pattern with varied intensities. GLUT1 protein did not show any significant correlation with tumor stage and nodal metastasis (p+AD4-0.05 by Mann-Whitney test). However, the positive immunostaining for GLUT1 is associated with intestinal differentiation (p+AD0-0.003). Our results suggest that GLUT1 protein is associated with intestinal type of gastric cancer.
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Adulto , Idoso , Feminino , Humanos , Masculino , Adenocarcinoma/patologia , Adenocarcinoma , Mucosa Gástrica/patologia , Mucosa Gástrica , Intestinos , Metaplasia , Pessoa de Meia-Idade , Proteínas de Transporte de Monossacarídeos , Proteínas de Neoplasias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/patologia , Neoplasias Gástricas , Biomarcadores TumoraisRESUMO
Increased expression of glucose transporter1 (GLUT1) has been reported in many human cancers. We hypothesized that the degree of GLUT1 might provide a useful biological information in gastric adenocarcinoma. RT-PCR and immunostaining were used to analyze GLUT1 expression in gastric cancer. RT-PCR showed GLUT1 expression was not largely detected in normal gastric tissue but was detected in cancerous gastric tissue of counterpart. By immunohistochemistry, GLUT1 protein was absent in normal gastric epithelium and intestinal metaplasia. 11 of 65 patients with gastric adenocarcinoma had specific GLUT1 immunostaining in a plasma membrane pattern with varied intensities. GLUT1 protein did not show any significant correlation with tumor stage and nodal metastasis (p+AD4-0.05 by Mann-Whitney test). However, the positive immunostaining for GLUT1 is associated with intestinal differentiation (p+AD0-0.003). Our results suggest that GLUT1 protein is associated with intestinal type of gastric cancer.
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Adulto , Idoso , Feminino , Humanos , Masculino , Adenocarcinoma/patologia , Adenocarcinoma , Mucosa Gástrica/patologia , Mucosa Gástrica , Intestinos , Metaplasia , Pessoa de Meia-Idade , Proteínas de Transporte de Monossacarídeos , Proteínas de Neoplasias , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/patologia , Neoplasias Gástricas , Biomarcadores TumoraisRESUMO
Objective To investigate the protective effect of propofol on the brain against ischemia-reperfusion (I/R) injury. Methods Ninety healthy SD rats weighing 290-310g were randomly divided into 3 groups: Ⅰ propofol group (P) (n =42); Ⅱ normal saline group (NS) (n =42) and Ⅲ sham operation group (S) (n = 6). The animals were anesthetized with intraperitoneal 10% chloral hydrate 0.3 ml?100 g-1. Right external, internal and common carotid arteries were exposed. A nylon thread (0.25 mm in diameter) with rounded tip was inserted at the bifurcation into internal carotid artery and threaded cranially until resistance was felt. The distance from the bifurcation to the tip of the thread was about 17.5-18.5 mm. Middle cerebral artery occlusion (MCAO) was confirmed by ipsilateral Horner's sign and contralateral hemiplegia when the animals were awake after anesthesia. In group P propofol 10 mg?100 g-1 was given intraperitoneally (i .p. ) 10 min before MCAO which was maintained for 1 hour. In group NS, NS was given instead of propofol. In group S the carotid arteries were exposed but MCAO was not performed. Reperfusion was produced by withdrawal of the nylon thread. The animals were killed at 0,2, 5, 11, 23, 71 h and 1 week after reperfusion was started (6 animals at each time-point) . Brains were immediately removed and sliced. The infarct size was analyzed quantitatively by Kontron IBAS 2.5 image auto-analysis system. The glucose transporter-1 (GLUT-1) mRNA was assessed by RT-PCR. The expression of GLUT-1 protein was determined by immuno-histochemistry. Results The infarct size was significantly smaller in P group than in NS group. In P group GLUT-1 mRNA began to increase at Oh, peaked at 23 h and remained higher than normal at 1 week after reperfusion was started and was significantly higher than that in NS group at 0, 2, 5, 11, 23, 71 h and 1 week. The changes in expression of GLUT-1 protein corresponded with the changes in GLUT-1 mRNA.Conclusion Propofol can protect the brain from I/R injury to some extent when given before ischemia. Upregulation of GLUT-1 expression is involved in the mechanism.
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Objective Surgical stress induces a series of endocrine and metabolic changes including glucose metabolism and insulin-resistance. The purpose of the present study was to investigate the changes in glucose transporter-4 (Glut-4) mRNA expression in skeletal muscle after cholecystectomy under epidural block. Methods One gram of the rectus abdominis muscle was taken while abdomen was being opened and closed in patients undergoing cholecystectomy under epidural block. Total RNA of the muscle cells was extracted by trizol one-step template. RT-PCR was used to determine the Glut-4 mRNA amplification products with ?-actin mRNA as an internal control. The Glut-4 mRNA expression was expressed by (desired gene/ ?-actin?100% . The plasma glucose and insulin levels were determined at the same time. Results Glut-4 mRNA expression was significantly reduced (P 0.05 ) . Conclusions The results indicated that the synthesis of Glut-4 is suppressed by surgical stress of cholecystectomy under epidural block leading to insulin resistance.
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Objective To study the effect and mechanism of intensive insulin therapy on stress hyperglycemia in rabbits with sepsis. Methods Rabbits were subjected to cecal ligation plus puncture (CLP) to reproduce sepsis. Sixty rabbits were randomly divided into three groups, control group (n=12), CLP group, and intensive insulin therapy group (n=24). The following parameters were measured with the method indicated in parentheses: blood glucose (blood sugar meter), glucose transporter 4 (GluT4) mRNA expression (RT-PCR), GluT4 protein level (Western blot). Results Compare with the control group, the level of blood glucose was significantly increased at 2h after CLP and reached its peak 12h after CLP (P
