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J Biol Chem ; 280(38): 32625-33, 2005 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-16049004

RESUMO

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.


Assuntos
Plaquetas/enzimologia , Plaquetas/metabolismo , Glucose/farmacocinética , Azepinas/metabolismo , Azepinas/farmacologia , Transporte Biológico , Cálcio/metabolismo , Membrana Celular/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Citometria de Fluxo , Glucose/metabolismo , Humanos , Immunoblotting , Insulina/metabolismo , Cinética , Megacariócitos/metabolismo , Modelos Biológicos , Selectina-P/metabolismo , Fosforilação , Agregação Plaquetária , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina/química , Trombina/metabolismo , Trombina/farmacologia , Fatores de Tempo
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