title: Dipalmitoleoylphosphoethanolamine as a PP2A enhancer obstructs insulin signaling by promoting Ser/Thr dephosphorylation of Akt.
abstract: OBJECTIVE
  The phospholipid phosphatidylethanolamine is implicated in the regulation of a variety of cellular processes. The present study investigated the effect of phosphatidylethanolamines such as 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE), 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPE), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE) on protein phosphatases, Akt1/2 activity, GLUT4 mobilizations, and glucose uptake into cells.
  
  
  METHODS
  Activity of protein phosphatase 2A (PP2A) was assayed under the cell-free conditions, and Western blotting, intracellular GLUT4 trafficking, and glucose uptake into cells were monitored using differentiated 3T3-L1-GLUT4myc adipocytes.
  
  
  RESULTS
  Of the investigated phosphatidylethanolamines, DLPE and DPPE significantly enhanced PP2A activity. DPPE inhibited insulin-induced phosphorylation of Akt1/2 at Thr308/309 and Ser473/474 in differentiated 3T3-L1-GLUT4myc adipocytes. DPPE also inhibited insulin-stimulated GLUT4 translocation to the cell surface and reduced insulin-stimulated glucose uptake into adipocytes.
  
  
  CONCLUSIONS
  The results of the present study indicate that the PP2A enhancer DPPE obstructs insulin signaling by promoting serine/threonine dephosphorylation of Akt1/2, resulting in the suppression of GLUT4 translocation to the cell surface and glucose uptake into adipocytes.
authors.affiliation: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tsuchiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanno
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nishizaki
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D004789:Enzyme Activation; D004983:Ethanolamines / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D015398:Signal Transduction; D013912:Threonine / Q000378:metabolism*
chemical_list: D004983:Ethanolamines; D005231:Fatty Acids, Unsaturated; D007328:Insulin; C494000:dipalmitoleoylphosphatidylethanolamine; D013912:Threonine; D012694:Serine; D051057:Proto-Oncogene Proteins c-akt; D054648:Protein Phosphatase 2