Jejunal/kidney glucose transporter isoform (Glut-5) is expressed in the human blood-brain barrier

Mantych, G. J.

doi:10.1210/en.132.1.35

Cited by 20 publications

(10 citation statements)

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“…One reason for this confusion is that accessibility of fructose to brain cells has been difficult to quantify. The expression of GLUT5 in the blood-brain barrier (BBB) (Mantych et al, 1993) and microglial (Maher et al, 1994) allow fructose to enter the brain, but provides little insight into the concentrations attained physiologically. The ability of fructose to cross into cerebral spinal fluid of dogs has been investigated, though this study did not investigate other neural tissues, nor was metabolism of fructose measured (Fishman, 1963).…”

Section: Discussionmentioning

confidence: 99%

Specific regions of the brain are capable of fructose metabolism

2017

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High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and nonalcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40–60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5–10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15–150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production.

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Section: Discussionmentioning

confidence: 99%

Specific regions of the brain are capable of fructose metabolism

2017

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“…These include members of the glucose transporters family Glut-1, Glut-2, Glut-3 and Glut-5 [39,40]; solute carriers specific for cationic aminoacids, organic anions and cations, folate, sulfate as well as the Na-K-Cl symporter and the potassium-chloride cotransporter. All together these specialized functions represent the hallmark of a drastic differentiation process that set the brain microcapillary endothelium aside from those forming other vascular beds.…”

Section: Discussionmentioning

confidence: 99%

The role of shear stress in Blood-Brain Barrier endothelial physiology

et al. 2011

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BackgroundOne of the most important and often neglected physiological stimuli contributing to the differentiation of vascular endothelial cells (ECs) into a blood-brain barrier (BBB) phenotype is shear stress (SS). With the use of a well established humanized dynamic in vitro BBB model and cDNA microarrays, we have profiled the effect of SS in the induction/suppression of ECs genes and related functions.ResultsSpecifically, we found a significant upregulation of tight and adherens junctions proteins and genes. Trans-endothelial electrical resistance (TEER) and permeability measurements to know substances have shown that SS promoted the formation of a tight and highly selective BBB. SS also increased the RNA level of multidrug resistance transporters, ion channels, and several p450 enzymes. The RNA level of a number of specialized carrier-mediated transport systems (e.g., glucose, monocarboxylic acid, etc.) was also upregulated.RNA levels of modulatory enzymes of the glycolytic pathway (e.g., lactate dehydrogenase) were downregulated by SS while those involved in the Krebs cycle (e.g., lactate and other dehydrogenases) were upregulated. Measurements of glucose consumption versus lactate production showed that SS negatively modulated the glycolytic bioenergetic pathways of glucose metabolism in favor of the more efficient aerobic respiration. BBB ECs are responsive to inflammatory stimuli. Our data showed that SS increased the RNA levels of integrins and vascular adhesion molecules. SS also inhibited endothelial cell cycle via regulation of BTG family proteins encoding genes. This was paralleled by significant increase in the cytoskeletal protein content while that of membrane, cytosol, and nuclear sub-cellular fractions decreased. Furthermore, analysis of 2D gel electrophoresis (which allows identifying a large number of proteins per sample) of EC proteins extracted from membrane sub-cellular endothelial fractions showed that SS increased the expression levels of tight junction proteins. In addition, regulatory enzymes of the Krebb's cycle (aerobic glucose metabolism) were also upregulated. Furthermore, the expression pattern of key protein regulators of the cell cycle and parallel gene array data supported a cell proliferation inhibitory role for SS.ConclusionsGenomic and proteomic analyses are currently used to examine BBB function in healthy and diseased brain and characterize this dynamic interface. In this study we showed that SS plays a key role in promoting the differentiation of vascular endothelial cells into a truly BBB phenotype. SS affected multiple aspect of the endothelial physiology spanning from tight junctions formation to cell division as well as the expression of multidrug resistance transporters. BBB dysfunction has been observed in many neurological diseases, but the causes are generally unknown. Our study provides essential insights to understand the role played by SS in the BBB formation and maintenance.

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“…Although researchers have been trying to better understand the fructose transport process from the blood to the brain, the collected data are still inconclusive. To date, GLUT5, which is the only fructose-specific facilitative glucose transporter [ 102 ], has been identified in the human BBB [ 103 ]. However, radiolabeled fructose injection into the rat common carotid artery resulted in no measurable uptake of fructose in the brain in the short period, suggesting the insignificant transport of fructose across the BBB [ 104 ].…”

Section: Fructose Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Chiba

Murakami

Matsumoto

et al. 2020

IJMS

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The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.

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Jejunal/kidney glucose transporter isoform (Glut-5) is expressed in the human blood-brain barrier

Cited by 20 publications

References 0 publications

Specific regions of the brain are capable of fructose metabolism

Specific regions of the brain are capable of fructose metabolism

The role of shear stress in Blood-Brain Barrier endothelial physiology

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

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