Blood—Brain Barrier Glucose Transporter

Simpson, Ian A.; Appel, Nathan M.; Hokari, Mitsuhiko; Oki, Jun; Holman, Geoffrey D.; Maher, Frances A.; Koehler-Stec, Ellen M.; Vannucci, Susan J.; Smith, Quentin R.

doi:10.1046/j.1471-4159.1999.0720238.x

Cited by 278 publications

(98 citation statements)

References 44 publications

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“…and sglt1 in cerebENDs after OGD and reoxygenation on the protein level (see supplementary figure 1) supporting our glucose uptake results and confirming data from the literature that glucose transporters are posttranscriptionally regulated by processes which can control mRNA stability, transporter concentrations at the luminal surface and their affinities to glucose [6,21]. Furthermore, presence and function of other glucose transporters at the BBB should not be neglected.…”

Section: Resultssupporting

confidence: 91%

Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells

Neuhaus

Burek

Djuzenova

et al. 2012

Neuroscience Letters

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During stroke the blood-brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7-fold after six hours OGD, which was significantly reduced by 10 µM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after six hours OGD and was still higher (210%) after the 20 hours reoxygenation phase compared to normoxia. Ten µM MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.

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Section: Resultssupporting

confidence: 91%

Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells

Neuhaus

Burek

Djuzenova

et al. 2012

Neuroscience Letters

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Section: Methodsmentioning

confidence: 99%

“…␥-glutamyltranspeptidase and System A amino acid transport activity with N-(methylamino)isobutyric acid as substrate, respectively (8). Rat microvessels and vascular-free rat brain membranes were prepared as previously described (15,16).Western Blot-Western blot analysis was performed as previously described (17) and quantified by chemiluminescence and image analysis (18). Human erythrocyte and rat brain membrane samples were included on all blots as internal GLUT1 standards for quantitation.…”

mentioning

confidence: 99%

Glucose Transporter Asymmetries in the Bovine Blood-Brain Barrier

Simpson¹,

Vannucci

DeJoseph

et al. 2001

Journal of Biological Chemistry

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The transport of glucose across the mammalian bloodbrain barrier is mediated by the GLUT1 glucose transporter, which is concentrated in the endothelial cells of the cerebral microvessels. Several studies supported an asymmetric distribution of GLUT1 protein between the luminal and abluminal membranes (1:4) with a significant proportion of intracellular transporters. In this study we investigated the activity and concentration of GLUT1 in isolated luminal and abluminal membrane fractions of bovine brain endothelial cells. Glucose transport activity and glucose transporter concentration, as determined by cytochalasin B binding, were 2-fold greater in the luminal than in the abluminal membranes. In contrast, Western blot analysis using a rabbit polyclonal antibody raised against the C-terminal 20 amino acids of GLUT1 indicated a 1:5 luminal:abluminal distribution. Western blot analysis with antibodies raised against either the intracellular loop of GLUT1 or the purified erythrocyte protein exhibited luminal:abluminal ratios of 1:1. A similar ratio was observed when the luminal and abluminal fractions were exposed to the 2-N-4 The mammalian brain depends on a continuous supply of glucose for normal function. The delivery of circulating glucose to the brain requires transport across the endothelial cells of the cerebral microvessels that constitute the blood-brain barrier (BBB).1 Glucose transport across the BBB is mediated by the highly glycosylated, 55-kDa form of the facilitative glucose transporter protein, GLUT1 (1, 2). The capacity for facilitated glucose transport across both the luminal (blood-facing) and abluminal (brain-facing) membranes of the endothelial cell was confirmed by electron microscopy immunolocalization studies, which reported GLUT1 protein in both luminal and abluminal membranes as well as in intracellular vesicles (3, 4). Most studies support an asymmetric distribution of GLUT1 among these three compartments: 11% luminal membrane, 44% abluminal membrane/vesicles, and 45% intracellular membrane/ vesicles for rat (4) with similar distributions reported for rabbit (5) and human (6). This apparent difference in GLUT1 concentrations between luminal and abluminal membranes could convey a polarity to BBB glucose transport favoring transport from the blood, across the endothelial cell, and into the brain. In addition, the existence of the intracellular pool and the potential for transporter recruitment and redistribution between membranes has been proposed as a mechanism underlying the acute modulations in brain glucose transport observed in vivo (7). The question of the rate-determining step in BBB glucose transport has been difficult to resolve because of the inability to study the transport properties of the luminal and abluminal membranes separately. Hawkins and colleagues (8 -10) developed a methodology to separate luminal and abluminal membranes to specifically address the kinetics of glucose and amino acid transport across the respective membranes. Utilizing this preparation, Lee et al. (11) ...

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“…It has been shown that both acute and chronic (both insulin-induced and fast-induced) hypoglycemia up-regulates genes for glucose uptake (GLUT1, AGT, ID1, and MKP) in the hypothalamus, thereby preserving the brain's need for glucose, and it also down-regulates the counterregulatory response (53,54). This phenomenon could be part of the explanation for the large number of asymptomatic hypoglycemias.…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Hypoglycemia in everyday life after gastric bypass and duodenal switch

Abrahamsson

Engström

Sundbom

et al. 2015

European Journal of Endocrinology

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Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (!3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P!0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

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Blood—Brain Barrier Glucose Transporter

Cited by 278 publications

References 44 publications

Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells

Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the upregulation of glucose uptake after subsequent reoxygenation in brain endothelial cells

Glucose Transporter Asymmetries in the Bovine Blood-Brain Barrier

Hypoglycemia in everyday life after gastric bypass and duodenal switch

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