Differential Glucose Uptake in Retina- and Brain-Derived Endothelial Cells

Rajah, Talitha T.; Olson, Ann Louise; Grammas, Paula

doi:10.1006/mvre.2001.2337

Cited by 42 publications

(22 citation statements)

References 25 publications

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“…The same study detected 7.26 fmol GLUT1/g PM protein in HUVECs, while the levels of other GLUT transporters were below detection, confirming the dominant position of GLUT1 in endothelial cells. On the other hand, our study, as well as others [59,60], identified additional GLUT transporters as relevant for glucose uptake in the endothelium. In particular GLUT3, even if less abundant at the protein level, could significantly contribute to endothelial glucose uptake because of its rapid turnover and high affinity for glucose, especially relevant in hypoglycemic conditions.…”

Section: Discussionmentioning

confidence: 78%

“…However, similar treatment was found to decrease glucose uptake in bovine aortic EC [67]. Bovine brain and rat heart endothelial cells exposed to 30 mM glucose for 1-3 days reduced their glucose uptake while bovine retinal endothelial cells remained quite unresponsive to increased glucose concentration even after 3 days [60], suggesting differences in the response depending on the species or cell origin. We have observed a moderate decrease in deoxy-glucose uptake in the chronically treated mature endothelial monolayers as a result of downregulation of total GLUT3 and cell surface GLUT1, while no major changes in GLUT mRNA expression were detected.…”

Section: Discussionmentioning

confidence: 88%

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Transendothelial glucose transport is not restricted by extracellular hyperglycaemia

Tumova

Kerimi

Porter

et al. 2016

Vascular Pharmacology

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Endothelial cells are routinely exposed to elevated glucose concentrations post-prandially in healthy individuals and permanently in patients with metabolic syndrome and diabetes, and so we assessed their sugar transport capabilities in response to high glucose. In human umbilical vein (HUVEC), saphenous vein, microdermal vessels and aorta, GLUT1 (SLC2A1), GLUT3 (SLC2A3), GLUT6 (SLC2A6), and in microdermal vessels also GLUT12 (SLC2A12), were the main glucose transporters as assessed by mRNA, with no fructose transporters nor SGLT1 (SLC5A1). Uptake of 14 C-fructose was negligible. GLUT1 and GLUT3 proteins were detected in all cell types and were responsible for ~60% glucose uptake in HUVECs, where both GLUT1 and GLUT3, but not GLUT6 siRNA knock-down, reduced the transport. Under shear conditions, GLUT1 protein decreased, GLUT3 increased, and 14 C-deoxy-glucose uptake was attenuated. In high glucose, lipid storage was increased, cell numbers were lower, 14 C-deoxyglucose uptake decreased owing to attenuated GLUT3 protein and less surface GLUT1, and transendothelial transport of glucose increased due to cell layer permeability changes. We conclude that glucose transport by endothelial cells is relatively resistant to effects of elevated glucose. Cells would continue to supply it to the underlying tissues at a rate proportional to the blood glucose concentration, independent of insulin or fructose.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 88%

Transendothelial glucose transport is not restricted by extracellular hyperglycaemia

Tumova

Kerimi

Porter

et al. 2016

Vascular Pharmacology

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“…For instance, bovine retinal endothelial cells maintained a constant level of glucose uptake throughout a 72-h incubation period at either 5.0 or 30.0 mmol/l glucose, while bovine brain and rat heart endothelial cells already downregulated glucose transport within 24 h of exposure to 30.0 mmol/l glucose [9]. Thus, various types of VEC, such as macro-and microvascular, may respond differently to hyperglycaemic conditions.…”

Section: Discussionmentioning

confidence: 99%

Delayed autoregulation of glucose transport in vascular endothelial cells

Alpert

Gruzman²,

Riahi³

et al. 2005

Diabetologia

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Aims/hypothesis: We aimed to characterise the development of autoregulation of glucose transport in vascular endothelial cells and its relationship to 12-lipoxygenase (12-LO) expression. Methods: Bovine aortic endothelial cells were exposed to 5.5 and 23.0 mmol/l glucose for up to 48 h. The rates of glucose transport, GLUT-1 and 12-LO expression and of 12-hydroxyeicosatetraenoic acid (12-HETE) production were determined. Results: We showed high glucose-dependent downregulation of glucose transport and transporter in vascular endothelial cells within 36-48 h. A similar time-dependent increase in the expression of 12-LO and the generation of its product 12-HETE was also observed. This downregulatory process was prevented when lipoxygenase activity was inhibited. Conclusions/interpretation: Vascular endothelial cells, which were previously thought to be "glucose-blind", do in fact downregulate GLUT-1 expression and the rate of glucose transport in response to extended exposure to high glucose concentrations. This slow development of glucose-induced downregulation in vascular endothelial cells is related to the slower basal rate of glucose transport in these cells and the slow induction of 12-LO.These data are interesting in view of current hypotheses that attribute vascular endothelial cell dysfunction in diabetes to the lack of a glucose-induced autoregulatory response.

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“…Although it has been held that vascular EC are "glucose-blind" and lack the ability to decrease glucose transport in response to elevated glucose levels, recent data have shown that exposure to high glucose results in decreased GLUT-1 expression and reduced glucose uptake in EC from various tissues, including brain and heart (15,16). In this manner, it is proposed that the endothelium senses and responds to blood glucose (BG) levels and coordinates these with parenchymal cell glucose delivery and metabolism.…”

mentioning

confidence: 99%

Normal glucose uptake in the brain and heart requires an endothelial cell-specific HIF-1α–dependent function

Huang

Liu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Although intimately positioned between metabolic substrates in the bloodstream and the tissue parenchymal cells that require these substrates, a major role of the vascular endothelium in the regulation of tissue metabolism has not been widely appreciated. We hypothesized that via control of transendothelial glucose transport and contributing paracrine mechanisms the endothelium plays a major role in regulating organ and tissue glucose metabolism. We further hypothesized that the hypoxia-inducible factor -1α (HIF-1α) plays an important role in coordinating these endothelial functions. To test these hypotheses, we generated mice with endothelial cell-specific deletion of HIF-1α. Loss of HIF in the endothelium resulted in significantly increased fasting blood glucose levels, a blunted insulin response with delayed glucose clearance from the blood after i.v. loading, and significantly decreased glucose uptake into the brain and heart. Endothelial HIF-1α knockout mice also exhibited a reduced cerebrospinal fluid/blood glucose ratio, a finding consistent with reduced transendothelial glucose transport and a diagnostic criterion for the Glut1 deficiency genetic syndrome. Endothelial cells from these mice demonstrated decreased Glut1 levels and reduced glucose uptake that was reversed by forced expression of Glut1. These data strongly support an important role of the vascular endothelium in determining whole-organ glucose metabolism and indicate that HIF-1α is a critical mediator of this function.transcription | transporter | microvascular

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Differential Glucose Uptake in Retina- and Brain-Derived Endothelial Cells

Cited by 42 publications

References 25 publications

Transendothelial glucose transport is not restricted by extracellular hyperglycaemia

Transendothelial glucose transport is not restricted by extracellular hyperglycaemia

Delayed autoregulation of glucose transport in vascular endothelial cells

Normal glucose uptake in the brain and heart requires an endothelial cell-specific HIF-1α–dependent function

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