GLUT-3 (brain-type) glucose transporter polypeptides in human blood platelets

Craik, James D.; Stewart, Michael; Cheeseman, Chris I.

doi:10.1016/0049-3848(95)00136-f

Cited by 33 publications

(23 citation statements)

References 26 publications

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“…It was, therefore, of interest to determine which GLUTs are responsible for mediating glucose uptake. A preliminary study by Craik et al [14] suggested that GLUT3 might be present in platelets. GLUT3 is generally considered to be the neuronal glucose transporter, although it has been detected in peripheral cells with high metabolic activity, e.g.…”

Section: Introductionmentioning

confidence: 98%

Thrombin-induced translocation of GLUT3 glucose transporters in human platelets

Sorbara

Davies-Hill

Koehler-Stec

et al. 1997

Biochemical Journal

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Platelets derive most of their energy from anaerobic glycolysis; during activation this requirement rises approx. 3-fold. To accommodate the high glucose flux, platelets express extremely high concentrations (155±18 pmol/mg of membrane protein) of the most active glucose transporter isoform, GLUT3. Thrombin, a potent platelet activator, was found to stimulate 2-deoxyglucose transport activity 3-5-fold within 10 min at 25 °C, with a half-time of 1-2 min. To determine the mechanism underlying the increase in glucose transport activity, an impermeant photolabel, [2-3H]2N-4-(1-azi-2,2,2-trifluoethyl)benzoyl-1,3,-bis-(d-mannose-4-ylozy)-2-propylamine, was used to covalently bind glucose transporters accessible to the extracellular milieu. In response to thrombin, the level of transporter labelling increased 2.7-fold with a half-time of 1-2 min. This suggests a translocation of GLUT3 transporters from an intracellular site to the plasma membrane in a manner analogous to that seen for the translocation of GLUT4 in insulin-stimulated rat adipose cells. To investigate whether a similar signalling pathway was involved in both systems, platelets and adipose cells were exposed to staurosporin and wortmannin, two inhibitors of GLUT4 translocation in adipose cells. Thrombin stimulation of glucose transport activity in platelets was more sensitive to staurosporin inhibition than was insulin-stimulated transport activity in adipose cells, but it was totally insensitive to wortmannin. This indicates that the GLUT3 translocation in platelets is mediated by a protein kinase C not by a phosphatidylinositol 3-kinase mechanism. In support of this contention, the phorbol ester PMA, which specifically activates protein kinase C, fully stimulated glucose transport activity in platelets and was equally sensitive to inhibition by staurosporin. This study provides a cellular mechanism by which platelets enhance their capacity to import glucose to fulfil the increased energy demands associated with activation.

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Section: Introductionmentioning

confidence: 98%

Thrombin-induced translocation of GLUT3 glucose transporters in human platelets

Sorbara

Davies-Hill

Koehler-Stec

et al. 1997

Biochemical Journal

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“…Activation of the white cells with either PMA or the appropriate activator, e.g., lipopolysaccharide (LPS) and formylmethionyl-leucyl-phenylalanine (fMLP) for neutrophils and monocytes/macrophages, phytohemagglutinin (PHA) for lymphocytes, and thrombin for platelets also results in the recruitment of GLUT3 to the plasma membrane (26,35,38,50,53,83,112). Figure 7 depicts the activation of neutrophils and platelets and the recruitment of GLUT3 to the respective plasma membranes.…”

Section: Glut3 In Human White Blood Cellsmentioning

confidence: 99%

The facilitative glucose transporter GLUT3: 20 years of distinction

Simpson

Dwyer

Malide

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

397

322

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Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: [15245][15246][15247][15248] 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells.neurons; sperm; preimplantation embryo; white blood cells GLUCOSE METABOLISM IS VITAL to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3 which, as implied by its name, was the third glucose transporter to be cloned (62) and was originally designated as the neuronal glucose transporter. Together with GLUT1, -2, and -4, it comprises the Class 1 group of transporters (For review see Refs. 15,81,121). With the cloning of GLUT3, it became apparent that the brain did not rely exclusively on GLUT1 and that GLUT3 was highly and specifically expressed by neurons. Thus, GLUT3 became the third facilitative glucose transporter isoform with unique characteristics suited for cell-specific expression and function. GLUT2 is ideally suited for expression in liver and pancreas due to its high K m for glucose; GLUT4 and its translocation from intracellular vesicles to the cell surface facilitates insulin-stimulated glucose uptake in insulin-sensitive cells: muscle and fat. The overriding question that drove the early work in GLUT3 in the brain was: why would neurons need a separate glucose transporter isoform; what is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand?...

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“…Neurons contain insulinindependent GLUT3 and GLUT1 glucose transporters (8 ); therefore, streptozotocin-evoked diabetic hyperglycemia increases conversion of glucose to pyruvate and acetylCoA and stimulates acetylcholine synthesis in brain nerve terminals (7 ). Like neurons, uptake of glucose into blood platelets is independent of insulin and is mediated through GLUT3 (9 ). It has been shown that diabetic hyperglycemia significantly increases the activity of key glucose and acetylCoA metabolism enzymes, including hexokinase, ACL, and PDH in platelets (10 ).…”

mentioning

confidence: 99%

Effect of l-Carnitine on Acetyl-CoA Content and Activity of Blood Platelets in Healthy and Diabetic Persons

et al. 2005

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Background: Excessive blood platelet activity contributes to vascular complications in diabetic persons. Increased acetyl-CoA in platelets from diabetic persons has been suggested to be a cause of this hyperactivity. We therefore investigated whether L-carnitine, which up-regulates metabolism of acetyl-CoA in muscles and brain, may affect platelet function in healthy and diabetic individuals. Methods: We obtained platelets from healthy and diabetic persons and measured acetyl-CoA concentrations, malonyl dialdehyde (MDA) synthesis, and platelet aggregation in the absence and presence of L-carnitine. Activities of selected enzymes involved in glucose and acetyl-CoA metabolism were also assessed. Results: Fasting glucose, fructosamine, and hemoglobin A 1c were present in significantly higher amounts in the blood of diabetic patients than in healthy individuals. Activities of carnitine acetyltransferase, glucose-6-phosphate dehydrogenase, oxoglutarate dehydrogenase, and fatty acid synthase were 17%-62% higher in platelets from diabetic patients. Mitochondrial acetyl-CoA was increased by 98% in platelets from diabetic patients, MDA synthesis was increased by 73%, and platelet aggregation by 60%. L-Carnitine had no or only a slight effect on these indices in platelets from healthy individuals, but in platelets from diabetic patients, L-carnitine caused a 99% increase in acetyl-CoA in the cytoplasmic compartment along with increases in MDA synthesis and platelet aggregation.

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GLUT-3 (brain-type) glucose transporter polypeptides in human blood platelets

Cited by 33 publications

References 26 publications

Thrombin-induced translocation of GLUT3 glucose transporters in human platelets

Thrombin-induced translocation of GLUT3 glucose transporters in human platelets

The facilitative glucose transporter GLUT3: 20 years of distinction

Effect of l-Carnitine on Acetyl-CoA Content and Activity of Blood Platelets in Healthy and Diabetic Persons

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