Involvement of Phospholipids in the Mechanism of Insulin
Action in HEPG2 Cells
R. NOVOTNÁ, P. DE VITO1,
L. CURRADO1, P. LULY1, P.M. BALDINI1
Department of Physiology and Developmental Biology,
Charles University, Prague, Czech Republic and 1Department
of Biology, University of Rome „Tor Vergata“, Rome, Italy
Received
March 22, 2002
Accepted September 6, 2002
Summary
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.
Key
words
Insulin • Phosphatidic acid • Diacylglycerol •
Phospholipases • HEPG2 cells
Reprint
requests
Dr. R. Novotná, Department of
Physiology and Developmental Biology, Charles University, 128 00
Prague 2, Viničná 7, Czech Republic. E-mail:
novotna2@natur.cuni.cz
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