共查询到19条相似文献,搜索用时 203 毫秒
1.
葡萄糖是中枢神经系统主要的能源物质,葡萄糖转运体(glucose transporter proteins,GLUTs)家族是哺乳动物细胞葡萄糖转运的主要载体,目前发现有13个成员。基于序列的相似性和同源性,GLUTs家族分为三类,第一类:GLUT1~GLUT4,主要运输葡萄糖;第二类:GLUT5,GLUT7,GLUT9和GLUT11,主要转运果糖;第三类:GLUT6,GLUT8,GLUT10,GLUT12和HMIT,其功能尚不清楚。其中GLUT1以异构体的形式广泛存在于多种细胞,但45 000GLUT1是介导葡萄糖跨血脑屏障的主要转运体。一些中枢神经系统疾病使GLUT1表达和功能改变,从而使糖转运过程受到干扰或糖代谢功能障碍。近来研究显示,GLUT1能介导经糖基化修饰的前体药物跨膜运输,因此,靶向于葡萄糖转运体跨血脑屏障的运载方法将会引起研究者更广泛的关注。 相似文献
2.
3.
4.
葡萄糖转运蛋白是细胞膜上的跨膜糖蛋白,介导细胞内外的葡萄糖以易化扩散的方式相互转运,是目前研究最为彻底的易化扩散转运体.葡萄糖的易化转运体家族到目前为止已有6种葡萄糖转运蛋白被鉴定,分别命名为葡萄糖转运蛋白-1~5(Glut-1~5)和葡萄糖转运蛋白-7(Glut-7),它们各自的功能取决于细胞的类型与代谢状态[1,2].现将Glut-1的生物特性及临床意义综述如下. 相似文献
5.
葡萄糖转运蛋白是细胞膜上的跨膜糖蛋白,介导细胞内外的葡萄糖以易化扩散的方式相互转运,是目前研究最为彻底的易化扩散转运体。葡萄糖的易化转运体家族到目前为止已有6种葡萄糖转运蛋白被鉴定,分别命名为葡萄糖转运蛋白-1~5(Glut-1~5)和葡萄糖转运蛋白-7(Glut-7),它们各自的功能取决于细胞的类型与代谢状态。现将Glut-1的生物特性及临床意义综述如下。 相似文献
6.
众所周知,葡萄糖作为细胞内各种组成成分的底物是一种最重要的能量来源,组织细胞摄入葡萄糖需借助胞膜上的葡萄糖转运蛋白(GLUT)载体.近年来,有关葡萄糖转运体家族(glucose transporters,GLUTs)的分子结构、生物学活性、临床意义等方面有大量的研究报道,尤其是其在恶性肿瘤中普遍高表达,与细胞的恶性转化、增殖、侵袭能力等密切相关,是目前肿瘤研究的热点.作者着重对葡萄糖转运蛋白1(GLUT1)及其与肿瘤的关系做一简介. 相似文献
7.
肾脏是人体最重要的排泄器官。肾单元近端小管细胞具有多种药物转运体和代谢酶,在药物及其代谢物处置中发挥关键作用。近端小管细胞中主要转运体包括有机阴离子转运体、有机阳离子转运体、有机阳离子/肉毒碱转运体、多药及毒素外排转运蛋白、P-糖蛋白、乳腺癌耐药蛋白和多药耐药相关蛋白;主要代谢酶包括细胞色素P450酶,UDP-葡萄糖醛酸基转移酶、磺酸基转移酶、谷胱甘肽S-转移酶。肾脏转运体和/或代谢酶介导药物相互作用(DDIs)是临床关注的重要问题。肾脏转运体和代谢酶存在密切协作关系,在肾脏也存在多种相互作用现象(包括转运-转运相互作用,代谢-代谢相互作用和转运-代谢相互作用),其显著影响药物肾脏处置、临床疗效和肾毒性。本文系统阐述了这些相互作用对药物及其代谢物的肾脏排泄、药动学、DDIs和肾毒性的影响。今后需要进一步阐明肾脏转运-代谢相互作用机制,将有助于研究体内药物肾脏处置和DDIs,促进临床合理用药。 相似文献
8.
9.
葡萄糖转运体(GLUTs)是外周组织摄取葡萄糖的主要载体,目前发现共有14个成员。其中GLUT4被称为胰岛素敏感性转运蛋白,广泛分布于骨骼肌、心肌、脂肪等组织,是胰岛素作用下发挥主要转运能力的载体蛋白,与多种代谢性疾病密切相关。多囊卵巢综合征(polycystic ovary syndrome,PCOS)是一种以闭经、不孕、肥胖、多毛为主要特征的内分泌紊乱性疾病,其发病机制不详。据报道,GLUT4与PCOS的生殖功能障碍及代谢异常密切相关,本综述主要概括GLUT4表达和功能变化与PCOS病理状态的关系,及这些改变对疾病产生的影响,并初步探讨了相关机制。 相似文献
10.
11.
Glucose transporter expression in the central nervous system: relationship to synaptic function 总被引:23,自引:0,他引:23
The family of facilitative glucose transporter (GLUT) proteins is responsible for the entry of glucose into cells throughout the periphery and the brain. The expression, regulation and activity of GLUTs play an essential role in neuronal homeostasis, since glucose represents the primary energy source for the brain. Brain GLUTs exhibit both cell type and region specific localizations suggesting that the transport of glucose across the blood–brain barrier is tightly regulated and compartmentalized. As seen in the periphery, insulin-sensitive GLUTs are expressed in the brain and therefore may participate in the central actions of insulin. The aim of this review will be to discuss the localization of GLUTs expressed in the central nervous system (CNS), with a special emphasis upon the recently identified GLUT isoforms. In addition, we will discuss the regulation, activity and insulin-stimulated trafficking of GLUTs in the CNS, especially in relation to the centrally mediated actions of insulin and glucose. 相似文献
12.
Increased need for glycolysis and glucose uptake for ATP production is observed in tumor cells, particularly in cells lacking of oxygen supply. Because glucose is transported from blood to tumor, glucose molecules must be delivered across glucose transporters of the vascular endothelium and tumor cells. Here we found that glioma suffered from hypoxic insults can secrete factor(s) to regulate glucose transporter expression in brain endothelium. It was found that conditioned medium from rat C6 glioma cells under hypoxia up-regulated glucose transporter type 1 (GLUT1) expression in rat brain endothelial cells, whereas conditioned medium from C6 cells under normoxia caused no significant effect. We further investigated whether the observed potentiating effect was caused by vascular endothelial growth factor (VEGF) production from C6 cells, because secreted VEGF was markedly increased under hypoxic condition. By transfection of C6 cells with VEGF small interfering RNA, it was found that conditioned medium from transfected cells under hypoxia no longer up-regulated GLUT1 expression of endothelial cells. Moreover, the addition of VEGF-neutralizing antibody to the hypoxic conditioned medium could also exert similar inhibitory effects. Furthermore, it was found that the VEGF-induced increase of GLUT1 expression in endothelial cells was mediated by the phosphoinositide-3 kinase/Akt pathway. Our results indicate that hypoxic brain glioma may secrete VEGF to increase glucose transport across blood-brain barrier. 相似文献
13.
Facilitative glucose transporter 1 (GLUT1) is the molecule responsible for the entry of glucose into the brain, and its mutation is known as GLUT1 deficiency syndrome (GLUT1DS) in humans. To clarify the effect of GLUT1 gene deficiency, we have produced GLUT1-deficient mice, and investigated the developmental expression of GLUT1, monocarboxylate transporter 1 (MCT1) and MCT2 in the brains of these mice. Since the homozygotes were found to be embryonically lethal and the heterozygotes exhibited no abnormalities, GLUT1deficiency was examined using heterozygote mice. GLUT1 deficiency did not significantly affect the mRNA levels of GLUT1 at P0, P7 and in adults, or the levels of MCTs at P7, P14 and in adults. The GLUT1 level at P14 was reduced by 46.9%, although this was not statistically significant. The MCTs levels at P0 were increased about 2.0-fold in the deficient mice compared with the wild type. Furthermore, at P0, GLUT1 mRNA levels in wild type females were 1.91-fold higher than in wild type males. These results suggest that GLUT1 deficiency affects GLUT1 mRNA expression in the infant brain, and that of MCT1 and MCT2 in the neonatal brain. Furthermore, a compensatory effect of GLUT1 expression was observed in the brain of adult deficient mice. These effects of GLUT1 deficiency in the brain provide a molecular basis to assist in our understanding of the symptoms of GLUT1DS. 相似文献
14.
Umeki N Fukasawa Y Ohtsuki S Hori S Watanabe Y Kohno Y Terasaki T 《Drug metabolism and pharmacokinetics》2002,17(4):367-373
An in vitro cell culture system for estimating the human blood-brain barrier (BBB) permeability of drugs is required for the development of drugs with effects on the central nervous system. In this study, cultured human brain microvascular endothelial cells (hBME) were characterized. hBME cells exhibited concentration-dependent uptake of L-Leu, L-Glu and L-Lys with K(m) values of 51.1+/-23.1 microM, 163.3+/-79.8 microM and 72.4+/-56.6 microM, respectively. The cellular accumulation of rhodamine123 in hBME cells was unaffected by P-glycoprotein (P-gp) substrates (cyclosporin A, quinidine and verapamil), while the accumulation in human P-gp-overexpressing cells was significantly increased in the presence of these P-gp substrates. RT-PCR revealed that hBME cells expressed large neutral amino acid transporter 1 (LAT1) and its associated molecule (4F2hc), excitatory amino acid transporter 3 (EAAT3), cationic amino acid transporter 1 (CAT1), glucose transporter 1 (GLUT1), monocarboxylic acid transporter 1 (MCT1) and multidrug resistance-associated protein 1 (MRP1). However, no expression of multidrug resistance protein 1 (MDR1) was detected. The results suggest that these amino acid transporters are functionally expressed at the human BBB, and that hBME cells retain the in vivo BBB transport functions and expression characteristics. Consequently, hBME cells should be a useful tool for studies of the human BBB. 相似文献
15.
Dysglycemia and central nervous system (CNS) complications are the known adverse effects of fluoroquinolone antibiotics. Ciprofloxacin and levofloxacin are among the most prescribed antibiotics. In this study we demonstrate that ciprofloxacin and levofloxacin disturb glucose transport into HepG2 cells and such inhibition is associated with inhibited glucose transporter type 1 (GLUT1) function. When exposed to ciprofloxacin or levofloxacin at maximum plasma concentrations (Cmax) and 5× of Cmax concentrations, GLUT1 mRNA expression, cell surface GLUT1 protein expression and glucose uptake were significantly reduced. These findings imply that disturbed cellular glucose transport and GLUT1 function may underlie the dysglycemic and CNS effects of ciprofloxacin and levofloxacin. 相似文献
16.
The binding affinities of the glucose transporter isoforms GLUT1, GLUT2, and GLUT4 for the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and isobutylmethylxanthine (IBMX) were compared in membranes from human erythrocytes and rat brain containing the erythrocyte-type glucose transporter (GLUT1), in membranes from rat liver containing the liver-type glucose transporter (GLUT2), and in membranes from adipocytes and heart containing predominantly the adipose/muscle-type glucose transporter (GLUT4). The binding affinities of cytochalasin B for GLUT1 and GLUT4 were virtually identical (KD) in membranes from erythrocytes, 190 nM; in brain, 130 nM; in adipocytes, 160 nM; and in heart, 170 nM). In contrast, no specific glucose-inhibitable binding of cytochalasin B was detected in liver membranes. The binding affinity for forskolin of GLUT1 was significantly lower than that of GLUT4 (KD in erythrocytes, 2360 nM; Kl in brain, 4360 nM; and KD in adipocytes, 200 nM; and in heart, 210 nM); specific glucose-inhibitable binding to GLUT2 was not detectable. Like forskolin, the glucose transport inhibitors dipyridamole (Kl in adipocyte membranes, 1.2 microM; in erythrocytes, greater than 40 microM) and IMBX (Kl in adipocyte membranes, 60 microM; and in erythrocytes, greater than 500 microM) bound with higher affinity to GLUT4 than to GLUT1. These data demonstrate striking differences of GLUT1, GLUT2, and GLUT4 with respect to their binding affinity for the inhibitory ligands cytochalasin B, forskolin, dipyridamole, and IBMX. It is suggested that the complex differences result from interaction of more than one heterogeneous binding site at the glucose transporters with the inhibitory ligand. 相似文献
17.
《Expert opinion on therapeutic targets》2013,17(12):1411-1427
Primary hepatocellular carcinoma (HCC) is one of the most fatal cancers in humans with rising incidence in many regions around the world. Currently, no satisfactory curative pharmacological treatment is available, and the outcome is mostly poor. Recently, we have shown that the glucose transporter GLUT1 is increased in a subset of patients with HCC and functionally affects tumorigenicity. GLUT1 is a rate-limiting transporter for glucose uptake, and its expression correlates with anaerobic glycolysis. This phenomenon is also known as the Warburg effect and recently became of great interest, since it affects not only glucose uptake and utilization but also has an influence on tumorigenic features like metastasis, chemoresistance and escape from immune surveillance. Consistent with this, RNA-interference-mediated inhibition of GLUT1 expression in HCC cells resulted in reduced tumorigenicity. Together, these findings indicate that GLUT1 is a novel and attractive therapeutic target for HCC. This review summarizes our current knowledge on the expression and function of GLUT1 in HCC, available drugs/strategies to inhibit GLUT1 expression or function, and potential side effects of such therapeutic strategies. 相似文献
18.
Batrakova EV Zhang Y Li Y Li S Vinogradov SV Persidsky Y Alakhov VY Miller DW Kabanov AV 《Pharmaceutical research》2004,21(11):1993-2000
PURPOSE: The amphiphilic block copolymer Pluronic P85 (P85) increases the permeability of the blood-brain barrier (BBB) with respect to a broad spectrum of drugs by inhibiting the drug efflux transporter, P-glycoprotein (Pgp). In this regard, P85 serves as a promising component for CNS drug delivery systems. To assess the possible effects of P85 on other transport systems located in the brain, we examined P85 interactions with the glucose (GLUT1) and monocarboxylate (MCT1) transporters. METHODS: Polarized monolayers of primary cultured bovine brain microvessel endothelial cells (BBMEC) were used as an in vitro model of the BBB. 3H-2-deoxy-glucose and 14C-lactate were selected as GLUT1 and MCT1 substrates, respectively. The accumulation and flux of these substrates added to the luminal side of the BBMEC monolayers were determined. RESULTS: P85 has little effect on 3H-2-deoxy-glucose transport. However, a significant decrease 14C-lactate transport across BBMEC monolayers is observed. Histology, immunohistochemistry, and enzyme histochemistry studies show no evidence of P85 toxicity in liver, kidney, and brain in mice. CONCLUSIONS: This study suggests that P85 formulations do not interfere with the transport of glucose. This is, probably, due to compensatory mechanisms in the BBB. Regarding the transport of monocarboxylates, P85 formulations might slightly affect their homeostasis in the brain, however, without any significant toxic effects. 相似文献
19.
1 Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. 2 The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (P<0.01). Less potent nootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (P<0.001). 3 Piracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. 4 There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. 5 Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. 相似文献