Glucose Uptake via Glucose Transporter 3 by Human Platelets Is Regulated by Protein Kinase B

Ferreira, Irlando Andrade; Mocking, Astrid I.M.; Urbanus, Rolf T.; Varlack, Samantha; Wnuk, Monika; Akkerman, Jan-Willem Ν.

doi:10.1074/jbc.m507221200

Cited by 29 publications

(35 citation statements)

References 45 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

403

322

View full text Add to dashboard Cite

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?...

show abstract

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

403

322

View full text Add to dashboard Cite

show abstract

“…9,22 Platelets were treated with 1 nmol/L insulin and aggregation was initiated with collagen and ADP. In healthy subjects, 1 nmol/L insulin inhibited collagen-and ADPinduced aggregation to 76Ϯ11% and 75Ϯ8%, respectively (PϽ0.05).…”

Section: Absent Inhibition Of Collagen-and Adp-induced Platelet Aggrementioning

confidence: 99%

Platelet Inhibition by Insulin Is Absent in Type 2 Diabetes Mellitus

Ferreira

Mocking

Feijge

et al. 2006

ATVB

Self Cite

192

148

View full text Add to dashboard Cite

Objective-ADP-induced P2y 12 signaling is crucial for formation and stabilization of an arterial thrombus. We demonstrated recently in platelets from healthy subjects that insulin interferes with Ca 2ϩ increases induced by ADP-P2y 1 contact through blockade of the G-protein G i , and thereby with P2y 12 -mediated suppression of cAMP. Methods and Results-Here we show in patients with type 2 diabetes mellitus (DM2) that platelets have lost responsiveness to insulin leading to increased adhesion, aggregation, and procoagulant activity on contact with collagen. Using Ser 473 phosphorylation of protein kinase B as output for insulin signaling, a 2-fold increase is found in insulin-stimulated normal platelets, but in DM platelets there is no significant response. In addition, DM2 platelets show increased P2y 12 -mediated suppression of cAMP and decreased P2y 12 inhibition by the receptor antagonist AR-C69931MX. Key Words: P2y 12 receptor Ⅲ Ca 2ϩ regulation Ⅲ clopidogrel Ⅲ protein kinase B/Akt Ⅲ IRS-1 P latelet activation leads to release of components that initiate formation of a thrombus and start inflammatory responses that contribute to atherosclerosis. 1 Signaling through the P2y 12 receptor is crucial for formation and stabilization of a thrombus. 2,3 Inhibition of the P2y 12 receptor reduces collagen-induced adhesion, aggregation and thrombin generation. 3,4 Subjects with a P2y 12 deficiency have a bleeding tendency 3,5 and individuals with an increased P2y 12 receptor copy number have platelets with an increased responsiveness to agonists, and these subjects experience peripheral arterial thrombosis. 6 The CAPRIE trial shows that long-term administration of the P2y 12 antagonist clopidogrel is more effective than aspirin in reducing the combined risk of ischemic stroke, myocardial infarction, or vascular death in subjects with a prothrombotic condition such as diabetes mellitus type 2 (DM2). 7 These findings illustrate the crucial role of P2y 12 signaling in platelet activation in vitro and in vivo. Conclusion-TheThe importance of P2y 12 signaling is explained by its capacity to initiate 2 pathways that directly interfere with platelet activating or inhibiting mechanisms. First, there is the activation of the G-protein subunit G i ␣, which inhibits adenylyl cyclase and thereby formation of the platelet inhibitor cAMP. 8 This property is particularly evident after treatment with prostacyclin, 9 and also in the absence of cAMP elevating agents, P2y 12 signaling controls cAMP production through adenylyl cyclase. 10,11 cAMP inhibits platelets through cAMPdependent protein kinase (protein kinase A [PKA]), 12 which inhibits almost all platelet functions through blockade of multiple steps in platelet activation cascades including receptor activation, signaling through the mitogen-activated protein kinases pathway, formation of thromboxane A 2 (TxA 2 ), and the activation of key enzymes such as phospholipase C ␤ and protein kinase C (PKC). 13 Second, there is the release of the G i ␤␥ dimer leading to the activation ...

show abstract

“…The mechanism underlying the increase of platelet size in response to hyperglycemia is similar to that described for the erythrocyte. In platelets, glucose uptake is also mediated by the facilitated diffusion protein GLUT3 (Ferreira et al, 2005). GLUT3 has high affinity for glucose (i.e., approximately 1.5 mmol/L), and it is hence predictable that a substantial increase of glucose in the extracellular fluid may be associated with gradual increase of intracellular glucose concentration, water influx and platelet swelling (Fig.…”

Section: Quality Specifications (%) Glucose Solution Contaminationmentioning

confidence: 99%

Influence of spurious dilution and hyperglycemia on erythrocytes and platelets evaluated with two different hematological analyzers

Lippi

Buonocore

Musa

et al. 2015

JAB

View full text Add to dashboard Cite

Available online xxx Keywords:Preanalytical variability Contamination Hyperglycemia Hematology Platelets Red blood cells a b s t r a c tThe integrity of whole blood samples may be compromised by suboptimal collection practices. Therefore, we investigated the influence of spurious hyperglycemia on erythrocytes and platelets, assessed with two hematological analyzers using optical or impedance technique. Three K 2 EDTA blood specimens were collected from 12 healthy subjects, pooled and divided into four aliquots. The first aliquot was left untreated (glucose concentration 4.4 mmol/L), whereas scalar amounts of standard 5% glucose solution were added to the remaining, generating glucose contamination of 5% (19.2 mmol/L), 10% (33 mmol/L) and 20%(62 mmol/L). Hematological testing was then performed using Siemens Advia 2120 and Sysmex XE-2100, whereas glucose and cell-free hemoglobin were measured in centrifuged plasma. Hemolysis did not occur in contaminated aliquots, whereas hemoglobin, erythrocyte count, hematocrit, mean corpuscular hemoglobin concentration and platelet count progressively decreased with glucose concentration. No clinically significant variation was found for red blood cell distribution width and mean corpuscular hemoglobin. The erythrocyte size increased in parallel with glucose, exhibiting larger variation with Advia 2120 than with XE-2100. The mean platelet volume increased on Advia 2120 but not on XE-2100. These results suggest that hyperglycemia induces alterations of erythrocyte and platelet properties, which differ according to the technology used for assessment.Please cite this article in press as: Lippi, G., et al., Influence of spurious dilution and hyperglycemia on erythrocytes and platelets evaluated with two different hematological analyzers. J. Appl. Biomed. (2015), http://dx.

show abstract

Glucose Uptake via Glucose Transporter 3 by Human Platelets Is Regulated by Protein Kinase B

Cited by 29 publications

References 45 publications

The facilitative glucose transporter GLUT3: 20 years of distinction

The facilitative glucose transporter GLUT3: 20 years of distinction

Platelet Inhibition by Insulin Is Absent in Type 2 Diabetes Mellitus

Influence of spurious dilution and hyperglycemia on erythrocytes and platelets evaluated with two different hematological analyzers

Contact Info

Product

Resources

About