葡萄糖转运蛋白基因多态性与糖尿病和糖尿病肾病的关系

目的：探讨葡萄糖转运蛋白（ＧＬＵＴ１）基因多态性与糖尿病及糖尿病肾病（ＤＮ）的关系。 方法：应用ＰＣＲ方法对１３１例Ⅱ型糖尿病（ＮＩＤＤＭ）患者ＧＬＵＴ１基因多态性与ＮＩＤＤＭ及ＤＮ发生之间的关系进行了观察，并结合患者体重指数（ＢＭＩ）和胰岛素敏感指数（ＩＳＩ）进行分析。 结果：①ＮＩＤＤＭ组患者Ｘｂａ Ｉ（＋／－）基因型的发生频率明显高于正常人群（６２％ｖｓ３３％，Ｐ〈０．０１），而Ｘｂａ Ｉ（     

小鼠肾小球系膜细胞葡萄糖转运蛋白的鉴定及其功能研究

目的：研究葡萄糖转运蛋白１（ｇｌｕｃｏｓｅｔｒａｎｓｐｏｒｔｏｒ，ＧＬＵＴ１）在肾小球系膜细胞上的表达与功能，探讨共在糖尿病肾病发病机制中的作用。方法：ＧＬＵＴ１ｍＲＮＡ蛋白质表达及其功能的检测分别采用ＲＴ－ＰＣＲ，细胞免疫荧光染色，流式细胞仪分析技术２－Ｄｅｏｘｙ－（＾３Ｈ）－Ｄ－Ｇｌｕｃｏｓｅ摄入法与根皮素竞争性抑制实验。结果：证实小鼠肾小球系膜细胞ＧＬＵＴ１ｍＲＮＡ和蛋白质的表达并表肯定了系     

强化胰岛素治疗对Ⅰ型糖尿病病人骨骼肌中胰岛素调节的葡萄糖转运蛋白（GLUT_4）表达的作用

强化胰岛素治疗对Ⅰ型糖尿病病人骨骼肌中胰岛素调节的葡萄糖转运蛋白（ＧＬＵＴ_４）表达的作用［ＡｎｄｅｒｓｅｎＰＨ，ｅｔａｌ．ＤｉａｂｅｔｉｃＭｅｄ，１９９３，１０：６９９］对正常人及啮齿动物的研究结果表明，骨骼肌中主要葡萄糖转运蛋白──ＧＬＵＴ４的表?..     

大黄酸对体外培养小鼠肾小球系膜细胞葡萄糖转运蛋白1表？…

目的 研究大黄酸对系膜细胞葡萄糖转运蛋白１（ＧＬＵＴ１）及葡萄糖摄入的影响,探讨大黄酸拮抗ＴＧＦβ１作用的可能机制。方法 选用体外培养的小鼠肾小球系膜细胞,ＧＬＵＴ１ｍＲＮＡ表达的检测采用Ｎｏｒｔｈｅｒｎ印迹,葡萄糖摄入的测定采用２－ｄｅｏｘｙ－〔＾３Ｈ〕－Ｄ－ｇｌｕｃｏｅｓ摄入法。结果 ＴＧＦβ１显著增加系膜细胞ＧＬＵＴ１ｍＲＮＡ的表达和葡萄糖摄入,大黄酸对正常培养条件下系膜细胞的葡萄糖摄入没有     

非胰岛素依赖型糖尿病肾病肾组织中EGF,EGF—R和IGF—1R的…

应用免疫组织化学定量分析的方法，对１２例胰岛素非依赖型糖尿病（ＮＩＤＤＭ）肾病患者肾活检组织中胰岛素样生长因子－１（ＩＧＧＦ－１）受体、表皮生长因子（ＥＧＦ）和表皮生长因子受体（ＥＧＦ－Ｒ）进行了观察，并结合患者的病程、糖尿病肾病分期和肾功能进行了比较。ＮＩＤＤＭ肾病患者肾小管上ＥＧＦ和ＥＧＦ－Ｒ的量明显高于正常人，部分患者肾小球ＥＧＦ也呈阳性反应。正常人和ＮＩＤＤＭ肾病患者肾小管上ＩＧＦ－１受体     

非胰岛素依赖型糖尿病肾病肾组织中EGF、EGF－R和IGF－1R的检测及其意义

应用免疫组织化学定量分析的方法，对１２例胰岛素非依赖型糖尿病（ＮＩＤＤＭ）肾病患者肾活检组织中胰岛素样生长因子－１（ＩＧＦ－１）受体、表皮生长因子（ＥＧＦ）和表皮生长因子受体（ＥＧＦ－Ｒ）进行了观察，并结合患者的病程、糖尿病肾病分期和肾功能进行了比较。ＮＩＤＤＭ肾病患者肾小管上ＥＧＦ和ＥＧＦ－Ｒ的量明显高于正常人，部分患者肾小球ＥＧＦ也呈阳性反应。正常人和ＮＩＤＤＭ肾病患者肾小管上ＩＧＦ－１受体的量则无明显差异。提示肾小管上ＥＧＦ和ＥＧＦ－Ｒ含量增加可能参与ＮＩＤＤＭ肾病的发病过程，而肾小球内ＥＧＦ的出现与系膜细胞和系膜基质增生有关。     

大黄酸对体外培养小鼠肾小球系膜细胞葡萄糖转运蛋白1表达及葡萄糖摄入的影响

目的　研究大黄酸对系膜细胞葡萄糖转运蛋白１（ Ｇ Ｌ Ｕ Ｔ１） 及葡萄糖摄入的影响,探讨大黄酸拮抗 Ｔ Ｇ Ｆβ１ 作用的可能机制。方法　选用体外培养的小鼠肾小球系膜细胞, Ｇ Ｌ Ｕ Ｔ１ ｍ Ｒ Ｎ Ａ表达的检测 采用 Ｎｏｒｔｈｅｒｎ 印迹, 葡萄糖摄入的测定采用２ｄｅｏｘｙ〔３ Ｈ〕 Ｄｇｌｕｃｏｓｅ 摄入法。结果 Ｔ Ｇ Ｆβ１ 显著增加系膜细胞 Ｇ Ｌ Ｕ Ｔ１ ｍ Ｒ Ｎ Ａ 的表达和葡萄糖摄入,大黄酸对正常培养条件下系膜细胞的葡萄糖摄入没有明显影响,但可以拮抗 Ｔ Ｇ Ｆβ１ 增加系膜细胞 Ｇ Ｌ Ｕ Ｔ１ ｍ Ｒ Ｎ Ａ 表达与葡萄糖摄入的作用。结论　 Ｔ Ｇ Ｆβ１ 介导系膜细胞葡萄糖代谢的改变以及细胞外基质合成的增加,大黄酸能明显抑制 Ｔ Ｇ Ｆβ１ 所引起的系膜细胞 Ｇ Ｌ Ｕ Ｔ１ 表达与葡萄糖摄入的异常增高。     

~（99m）Tc－DTPA肾动态显像测定GFR对糖尿病肾病早期诊断的价值

应用￣（９９ｍ）Ｔｃ－ＤＴＰＡ肾动态显像测定６１例ＮＩＤＤＭ的肾小球滤过率（ＧＦＲ），并与相配对的２０例正常人作比较。结果表明无蛋白尿的糖尿病患者ＧＦＲ，升高率为３５％，且与血糖呈正相关。提示￣（９９ｍ）Ｔｃ－ＤＴＰＡ肾动态显像测定ＧＦＲ可作为糖尿病肾病最早期诊断的检测手段。ＮＩＤＤＭ早期确实存在肾小球高滤状态．ＧＦＲ＞１４０ｍｌ／ｍｉｎ可作为糖尿病肾病发生的预兆指标。     

目前西方对肾小球肾炎的认识

在临床实践中，肾小球疾病是一种常见病，也是导致终末期肾病（ＤＳＲＤ）最常见的病因。美国１９９１～１９９５年的统计资料表明，在接受治疗的ＥＲＳＤ患者中，原发病因为肾小球疾病者占５１％，其中糖尿病肾病（ＤＮ）占３７－９％，非糖尿病肾小球疾病占１３－５％。在我国，导致ＥＳＲＤ的病因也以肾小球疾病为主，占５４－４％，但其中ＤＮ仅占４－７％，肾小球肾炎却占４８－１％。某些常见的肾小球疾病并不发展至肾衰，但仍是导致患者发病和医疗费支出的重要因素［１，２］。肾小球肾炎（ＧＮ）的病变特征为：组织学上表现为肾小球…     

尿系列微量蛋白对糖尿病肾病的诊断价值

采用双抗体夹心酶标免疫法（ＥＬＩＳＡ）及分光光度法，对７０例糖尿病（ＤＭ）患者随意新鲜１０ｍｌ尿中视黄醇结合蛋白（ＲＢＰ）、白蛋白（ＡＬＢ）、免疫球蛋白Ｇ（ＩｇＧ）、Ｎ－乙酰－β氨基葡萄糖苷酶（ＮＡＧ）的排泄率联合检测。结果表明，早期糖尿病肾病（ＤＮ）尿ＲＢＰ、ＡＬＢ、ＩｇＧ、ＮＡＧ增高，ＤＮ早期肾损害并非局限于肾小球，同时伴有肾小管病变。病程、年龄与肾损害的发生、发展及严重程度有关，提示联合检测ＤＭ患者尿系列微量蛋白有助于早期、确切判断并发肾病时病变部位及损伤程度。     

~(18)F-fluoro-2-deoxyglucose uptake on PET CT and glucose transporter 1 expression in colorectal adenocarcinoma

AIM:To evaluate the correlation between the level of 18 F-fluoro-2-deoxyglucose (18 F-FDG) uptake and glucose transporter 1 (GLUT1) expression in colorectal adenocarcinoma (CRA).METHODS:Forty four patients with resected CRA and preoperative 18 F-FDG positron emission tomography computed tomography data were investigated in this study.Comparison of maximum standardized uptake value (SUVmax) of the lesion was made with GLUT1 expression by immunohistochemistry and various clinicopathologic factors including tumor volume,invasion depth,gross finding,and lymph node metastasis.RESULTS:SUVmax was 14.45 ± 7.0 in negative GLUT1 expression cases,15.51 ± 5.7 in weak GLUT1 expression cases,and 16.52 ± 6.8 in strong GLUT1 expression cases,and there was no correlation between between GLUT1 expression and SUVmax.SUVmax was significantly correlated with tumor volume (P 0.001).However,there was no significant differences in SUVmax and GLUT1 expression among other clinicopathologic factors.CONCLUSION:GLUT1 expression does not correlates significantly with 18 F-FDG uptake in CRA.18 F-FDG uptake was increased with tumor volume,which is statistically significant.     

Glucose rapidly decreases plasma membrane GLUT4 content in rat skeletal muscle

We have previously demonstrated that chronic hyperglycemia per se decreases GLUT4 glucose transporter expression and plasma membrane content in mildly streptozotocin- (STZ) diabetic rats (Biochem. J. 284, 341-348, 1992). In the present study, we investigated the effect of an acute rise in glycemia on muscle GLUT4 and GLUT1 protein contents in the plasma membrane, in the absence of insulin elevation. Four experimental groups of rats were analyzed in the postabsorptive state: 1. Control rats. 2. Hyperglycemic STZ-diabetic rats with moderately reduced fasting insulin levels. 3. STZ-diabetic rats made normoglycemic with phlorizin treatment. 4. Phlorizin-treated (normoglycemic) STZ-diabetic rats infused with glucose for 40 min. The uniqueness of the latter model is that glycemia can be rapidly raised without any concomitant increase in plasma insulin levels. Plasma membranes were isolated from hindlimb muscle and GLUT1 and GLUT4 proteins amounts determined by Western blot analysis. As predicted, STZ-diabetes caused a significant decrease in the abundance of GLUT4 in the isolated plasma membranes. Normalization of glycemia for 3 d with phlorizin treatment restored plasma membrane GLUT4 content in muscle of STZ-diabetic rats. A sudden rise in glycemia over a period of 40 min caused the GLUT4 levels in the plasma membrane fraction to decrease to those of nontreated STZ-diabetic rats. In contrast to the GLUT4 transporter, plasma membrane GLUT1 abundance was not changed by the acute glucose challenge. It is concluded that glucose can have regulatory effect by acutely reducing plasma membrane GLUT4 protein contents in rat skeletal muscle. We hypothesize that this glucose-induced downregulation of plasma membrane GLUT4 could represent a protective mechanism against excessive glucose uptake under hyperglycemic conditions accompanied by insulin resistance.     

¹⁸F-fluoro-2-deoxyglucose uptake on PET CT and glucose transporter 1 expression in colorectal adenocarcinoma

AIM: To evaluate the correlation between the level of ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG) uptake and glucose transporter 1 (GLUT1) expression in colorectal adenocarcinoma (CRA).METHODS: Forty four patients with resected CRA and preoperative ¹⁸F-FDG positron emission tomography - computed tomography data were investigated in this study. Comparison of maximum standardized uptake value (SUVmax) of the lesion was made with GLUT1 expression by immunohistochemistry and various clinicopathologic factors including tumor volume, invasion depth, gross finding, and lymph node metastasis.RESULTS: SUVmax was 14.45 ± 7.0 in negative GLUT1 expression cases, 15.51 ± 5.7 in weak GLUT1 expression cases, and 16.52 ± 6.8 in strong GLUT1 expression cases, and there was no correlation between between GLUT1 expression and SUVmax. SUVmax was significantly correlated with tumor volume (P < 0.001). However, there was no significant differences in SUVmax and GLUT1 expression among other clinicopathologic factors.CONCLUSION: GLUT1 expression does not correlates significantly with ¹⁸F-FDG uptake in CRA. ¹⁸F-FDG uptake was increased with tumor volume, which is statistically significant.     

胰岛素对在体犬缺血心肌GLUT1基因表达呈协同作用

目的 :观察胰岛素对缺血心肌葡萄糖转运子 1(GLUT1)基因表达是否有协同作用。方法 :采用Northern法分析心肌GLUT1mRNA和免疫法分析心肌GLUT1多肽。结果 :输注胰岛素使局部低血流心肌GLUT1mRNA和GLUT1多肽表达增加 4 2～ 2倍。同时伴随心肌葡萄糖摄取明显增多。结论 :胰岛素对低血流缺血刺激心肌GLUT1mRNA和GLUT1多肽表达呈协同作用 ,其结果使心肌葡萄糖摄取量增多。胰岛素对低血流缺血刺激心肌GLUT1表达的协同作用 ,在缺血心肌能量代谢过程中起着重要的调节作用。     

Liraglutide enhances glucose transporter 4 translocation via regulation of AMP-activated protein kinase signaling pathways in mouse skeletal muscle cells

Objective

Liraglutide is an anti-diabetic drug and human glucagon-like peptide-1 (GLP-1) analog that primarily functions in the pancreas. However, its extra-pancreatic functions are not clear. Skeletal muscle tissue is an important determinant of blood glucose and cells take in approximately 80% of dietary glucose via glucose transporter 4 (GLUT4) on the plasma membrane. Insulin and muscle contraction are two physiological stimuli of GLUT4 translocation to the cell membrane from intracellular storage compartments, but the signaling mechanisms that mediate these processes are different. AMP-activated protein kinase (AMPK) and Akt are the key signal molecules mediating the effects of muscle contraction and insulin, respectively, on GLUT4 translocation. Here, we investigate the effect of liraglutide on GLUT4 translocation and the roles of AMPK and Akt in this mechanism in skeletal muscle cells by stably expressing GLUT4myc with an exofacial myc-epitope C₂C₁₂-GLUT4myc.

Materials/Methods

The cell surface GLUT4myc levels were determined by an antibody-coupled colorimetric assay. The phosphorylation levels of AMPK, Akt, AS160, TBC1D1, and GLUT4 were determined by western blotting. The cAMP levels were measured by an ELISA kit. siRNA was transfected with Lipofectamine 2000. Analysis of variance (ANOVA) was used for data analysis.

Results

Liraglutide stimulated GLUT4 translocation in C₂C₁₂-GLUT4myc myotubes. Liraglutide increased the intracellular cAMP levels and the phosphorylation of AMPK, AS160, and TBC1D1. Akt phosphorylation and GLUT4 expression were not affected. Inhibition of AMPK by siRNA or Compound C reduced liraglutide-induced GLUT4 translocation.

Conclusion

Our results suggest that liraglutide may induce GLUT4 translocation by activation of AMPK in muscle cells.     

叉头状转录因子O1对肥胖者内脏脂肪组织葡萄糖转运体4 mRNA及蛋白表达的影响

目的 利用RNAi技术沉默肥胖者内脏脂肪组织中叉头状转录因子O1(FOXO1)基因后检测葡萄糖转运体4(GLUT4)的mRNA和蛋白表达,探讨肥胖者FOXO1与胰岛素抵抗的关系及机制.方法 构建转录因子FOXO1特异性siRNA载体pSIREN-DNR-DsRed-siFOXO1(FOXO1-siRNA)质粒并鉴定;选取5例肥胖者大网膜脂肪组织利用脂质体为媒介转染FOXO1-siRNA质粒;半定量RT-PCR检测FOXO1 mRNA表达,测定抑制效率;半定量RT-PCR检测GLUT4 mRNA表达量,Westernblot检测GLUT4蛋白表达量.采用t检验进行统计分析.结果 成功构建FOXO1-siRNA质粒,转染此质粒的脂肪组织细胞FOXO1 mRNA表达水平与对照组相比下降约49%(P＜0.05),说明转染成功;FOXO1-siRNA质粒转染组GLUT4 mRNA较对照组增加约1.33倍(P=0.001),FOXO1-siRNA质粒转染组GLUT4蛋白较对照组增加约1.25倍(P＜0.05).结论 抑制肥胖者网膜内脏脂肪组织FOXO1基因的表达可引起GLUT4 mRNA及蛋白表达增加.