title: Glucose uptake via glucose transporter 3 by human platelets is regulated by protein kinase B.
abstract: In insulin-responsive tissues, insulin is a potent activator of protein kinase B (PKB)-mediated glucose uptake through the facilitative glucose transporter GLUT4. In platelets, glucose uptake is mediated through GLUT3, which is present in plasma (15%) and intracellular alpha-granule (85%) membranes. Here we report the PKB-mediated glucose uptake by platelets by agents that do (thrombin) or do not (insulin) induce alpha-granule translocation to the plasma membrane. Both thrombin and insulin activate PKB and induce glucose uptake albeit with different kinetics. Inhibition of PKB by the pharmacological inhibitor ML-9 decreases thrombin-induced alpha-granule release and thrombin- and insulin-induced glucose uptake. At low glucose (0.1 mm), both agents stimulate glucose uptake by lowering the Km for glucose (thrombin and insulin) and increasing Vmax (thrombin). At high glucose (5 mm), stimulation of glucose uptake by insulin disappears, and insulin becomes an inhibitor of thrombin-induced glucose uptake via mechanisms independent of PKB. We conclude that in platelets glucose transport through GLUT3 is regulated by changes in surface expression and affinity modulation, which are both under control of PKB.
authors.affiliation: Thrombosis and Haemostasis Laboratory, Department of Hematology, University Medical Center Utrecht.
authors.forename: Irlando Andrade
authors.initials: IA
authors.lastname: Ferreira
authors.forename: Astrid I M
authors.initials: AI
authors.lastname: Mocking
authors.forename: Rolf T
authors.initials: RT
authors.lastname: Urbanus
authors.forename: Samantha
authors.initials: S
authors.lastname: Varlack
authors.forename: Monika
authors.initials: M
authors.lastname: Wnuk
authors.forename: Jan-Willem N
authors.initials: JW
authors.lastname: Akkerman
mesh_terms: D001381:Azepines / Q000378:metabolism / Q000494:pharmacology; D001692:Biological Transport; D001792:Blood Platelets / Q000201:enzymology* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism; D007700:Kinetics; D008533:Megakaryocytes / Q000378:metabolism; D008954:Models, Biological; D019007:P-Selectin / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012694:Serine / Q000737:chemistry; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D007328:Insulin; D019007:P-Selectin; D012333:RNA, Messenger; C056218:ML 9; D012694:Serine; D013917:Thrombin; D005947:Glucose; D002118:Calcium