Testing the role of myeloid cell glucose flux in inflammation and atherosclerosis

Cell Rep. 2014 Apr 24;7(2):356-365. doi: 10.1016/j.celrep.2014.03.028. Epub 2014 Apr 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atherosclerosis / metabolism*
  • Biological Transport, Active
  • Cytokines / genetics
  • Cytokines / metabolism
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism*
  • Glycolysis
  • Inflammation / metabolism
  • Mice
  • Myeloid Cells / metabolism*
  • Pentose Phosphate Pathway
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism


  • Cytokines
  • Glucose Transporter Type 1
  • Receptors, LDL
  • Slc2a1 protein, mouse
  • Glucose