title: Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis.
abstract: Inflammatory activation of myeloid cells is accompanied by increased glycolysis, which is required for the surge in cytokine production. Although in vitro studies suggest that increased macrophage glucose metabolism is sufficient for cytokine induction, the proinflammatory effects of increased myeloid cell glucose flux in vivo and the impact on atherosclerosis, a major complication of diabetes, are unknown. We therefore tested the hypothesis that increased glucose uptake in myeloid cells stimulates cytokine production and atherosclerosis. Overexpression of the glucose transporter GLUT1 in myeloid cells caused increased glycolysis and flux through the pentose phosphate pathway but did not induce cytokines. Moreover, myeloid-cell-specific overexpression of GLUT1 in LDL receptor-deficient mice was ineffective in promoting atherosclerosis. Thus, increased glucose flux is insufficient for inflammatory myeloid cell activation and atherogenesis. If glucose promotes atherosclerosis by increasing cellular glucose flux, myeloid cells do not appear to be the key targets.
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishizawa
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Kanter
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Farah
authors.initials: F
authors.lastname: Kramer
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Shelley
authors.initials: S
authors.lastname: Barnhart
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Vivekanandan-Giri
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Valerie Z
authors.initials: VZ
authors.lastname: Wall
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Kowitz
authors.affiliation: Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Devaraj
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98109, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: O'Brien
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Radiology, University of Washington, Seattle, WA 98195, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Miyaoka
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA 98109, USA.
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Raines
authors.affiliation: Diabetes and Obesity Center of Excellence, University of Washington, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98109, USA; Department of Pathology, University of Washington, Seattle, WA 98109, USA. Electronic address: bornf@u.washington.edu.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Bornfeldt
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism*; D001693:Biological Transport, Active; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D006019:Glycolysis; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D022423:Myeloid Cells / Q000378:metabolism*; D010427:Pentose Phosphate Pathway; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D051272:Glucose Transporter Type 1; D011973:Receptors, LDL; C495678:Slc2a1 protein, mouse; D005947:Glucose
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