Involvement of phospholipids in the mechanism of insulin action in HEPG2 cells

• Published in: Physiological research Vol. 52; no. 4; pp. 447 - 454
• Main Authors: Novotná, R, De Vito, P, Currado, L, Luly, P, Baldini, P M
• Format: Journal Article
• Language: English
• Published: Czech Republic 2003
• Subjects: Carcinoma, Hepatocellular - metabolism; Cell Line, Tumor; Choline - metabolism; Chromatography, Thin Layer; Diglycerides - metabolism; Extracellular Space - drug effects; Extracellular Space - metabolism; Humans; Insulin - pharmacology; Insulin - physiology; Lipid Metabolism; Liver Neoplasms - metabolism; Phosphatidic Acids - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Phospholipids - physiology; Tetradecanoylphorbol Acetate - pharmacology
• DOI: 10.33549/physiolres.930305
• EISSN: 1802-9973
• ISSN: 0862-8408

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.