title: Ceramide 1-phosphate stimulates glucose uptake in macrophages.
abstract: It is well established that ceramide 1-phosphate (C1P) is mitogenic and antiapoptotic, and that it is implicated in the regulation of macrophage migration. These activities require high energy levels to be available in cells. Macrophages obtain most of their energy from glucose. In this work, we demonstrate that C1P enhances glucose uptake in RAW264.7 macrophages. The major glucose transporter involved in this action was found to be GLUT 3, as determined by measuring its translocation from the cytosol to the plasma membrane. C1P-stimulated glucose uptake was blocked by selective inhibitors of phosphatidylinositol 3-kinase (PI3K) or Akt, also known as protein kinase B (PKB), and by specific siRNAs to silence the genes encoding for these kinases. C1P-stimulated glucose uptake was also inhibited by pertussis toxin (PTX) and by the siRNA that inhibited GLUT 3 expression. C1P increased the affinity of the glucose transporter for its substrate, and enhanced glucose metabolism to produce ATP. The latter action was also inhibited by PI3K- and Akt-selective inhibitors, PTX, or by specific siRNAs to inhibit GLUT 3 expression.
authors: Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain.
authors: Alberto
authors: A
authors: Ouro
authors: Lide
authors: L
authors: Arana
authors: Patricia
authors: P
authors: Gangoiti
authors: Io-Guané
authors: IG
authors: Rivera
authors: Marta
authors: M
authors: Ordoñez
authors: Miguel
authors: M
authors: Trueba
authors: Ravi S
authors: RS
authors: Lankalapalli
authors: Robert
authors: R
authors: Bittman
authors: Antonio
authors: A
authors: Gomez-Muñoz
mesh_terms: D000818:Animals; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: D002518:Ceramides; D005947:Glucose; D051274:Glucose Transporter Type 3; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; C065576:ceramide 1-phosphate