Journal article
Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation
Arteriosclerosis, thrombosis, and vascular biology, Vol.37(9), pp.1628-1639
09/2017
DOI: 10.1161/ATVBAHA.117.309184
PMCID: PMC5570649
PMID: 28663252
Abstract
On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known about the role of glucose metabolism on platelet function in vivo. For glucose to enter a cell, it must be transported through glucose transporters. Here we evaluate the contribution of GLUT3 (glucose transporter 3) to platelet function to better understand glucose metabolism in platelets.
Platelet-specific knockout of GLUT3 was generated by crossing mice harboring GLUT3 floxed allele to a PF4 (platelet factor 4)-driven Cre recombinase. In platelets, GLUT3 is localized primarily on α-granule membranes and under basal conditions facilitates glucose uptake into α-granules to be used for glycolysis. After activation, platelets degranulate and GLUT3 translocates to the plasma membrane, which is responsible for activation-mediated increased glucose uptake. In vivo, loss of GLUT3 in platelets increased survival in a collagen/epinephrine model of pulmonary embolism, and in a K/BxN model of autoimmune inflammatory disease, platelet-specific GLUT3 knockout mice display decreased disease progression. Mechanistically, loss of GLUT3 decreased platelet degranulation, spreading, and clot retraction. Decreased α-granule degranulation is due in part to an impaired ability of GLUT3 to potentiate exocytosis.
GLUT3-mediated glucose utilization and glycogenolysis in platelets promotes α-granule release, platelet activation, and postactivation functions.
Details
- Title: Subtitle
- Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation
- Creators
- Trevor P Fidler - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Elizabeth A Middleton - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Jesse W Rowley - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Luc H Boudreau - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Robert A Campbell - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Rhonda Souvenir - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Trevor Funari - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Nicolas Tessandier - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Eric Boilard - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)Andrew S Weyrich - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.)E Dale Abel - From the Department of Pharmacology and Toxicology (T.P.F.), and Program in Molecular Medicine (T.P.F., E.A.M., J.W.R., R.A.C., A.S.W., E.D.A.), University of Utah, Salt Lake City; Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Carver College of Medicine, University of Iowa, Iowa City (T.P.F., R.S., T.F., E.D.A.); and Department of Infectious Diseases and Immunity, Centre de Recherche du Centre Hospitalier Universitaire de Québec and Faculté de Médecine de l'Université Laval, Quebec City, Canada (L.H.B., N.T., E.B.). DRCadmin@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Arteriosclerosis, thrombosis, and vascular biology, Vol.37(9), pp.1628-1639
- Publisher
- United States
- DOI
- 10.1161/ATVBAHA.117.309184
- PMID
- 28663252
- PMCID
- PMC5570649
- ISSN
- 1079-5642
- eISSN
- 1524-4636
- Grant note
- T32 DK091317 / NIDDK NIH HHS R01 HL126547 / NHLBI NIH HHS U01 HG004080 / NHGRI NIH HHS K01 GM103806 / NIGMS NIH HHS F32 HL128008 / NHLBI NIH HHS R01 GM103801 / NIGMS NIH HHS CIHR U54 HL112311 / NHLBI NIH HHS T32 DK007115 / NIDDK NIH HHS T32 HL007344 / NHLBI NIH HHS U42 OD012210 / NIH HHS T32 HL105321 / NHLBI NIH HHS U01 HG004085 / NHGRI NIH HHS U42 RR024244 / NCRR NIH HHS
- Language
- English
- Date published
- 09/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025289802771
Metrics
26 Record Views