title: Involvement of phospholipids in the mechanism of insulin action in HEPG2 cells.
abstract: The mechanism of action by which insulin increases phosphatidic acid (PA) and diacylglycerol (DAG) levels was investigated in cultured hepatoma cells (HEPG2). Insulin stimulated phosphatidylcholine (PC) and phosphatidyl-inositol (PI) degradation through the activation of specific phospholipases C (PLC). The DAG increase appears to be biphasic. The early DAG production seems to be due to PI breakdown, probably through phosphatidyl-inositol-3-kinase (PI3K) involvement, whereas the delayed DAG increase is derived directly from the PC-PLC activity. The absence of phospholipase D (PLD) involvement was confirmed by the lack of PC-derived phosphatidylethanol production. Experiments performed in the presence of R59022, an inhibitor of DAG-kinase, indicated that PA release is the result of the DAG-kinase activity on the DAG produced in the early phase of insulin action.
authors.affiliation: Department of Physiology and Developmental Biology, Charles University, 128 00 Prague 2, Vinicná 7, Czech Republic. novotna2@natur.cuni.cz
authors.forename: R
authors.initials: R
authors.lastname: Novotná
authors.forename: P
authors.initials: P
authors.lastname: De Vito
authors.forename: L
authors.initials: L
authors.lastname: Currado
authors.forename: P
authors.initials: P
authors.lastname: Luly
authors.forename: P M
authors.initials: PM
authors.lastname: Baldini
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D002794:Choline / Q000378:metabolism; D002855:Chromatography, Thin Layer; D004075:Diglycerides / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D050356:Lipid Metabolism; D008113:Liver Neoplasms / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010743:Phospholipids / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D007328:Insulin; D010712:Phosphatidic Acids; D010743:Phospholipids; D019869:Phosphatidylinositol 3-Kinases; D002794:Choline; D013755:Tetradecanoylphorbol Acetate