Metformin modulates insulin receptor signaling in normal and cholesterol-treated human hepatoma cells (HepG2)

Emmanuelle Meuillet, Nicolas Wiernsperger, Barbara Mania-Farnell, Pierre Hubert, Gerard Cremel

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The effects of the biguanide anti-hyperglycemic agent, metformin (N,N'-dimethyl-biguanide), on insulin signaling was studied in a human hepatoma cell line (HepG2). Cells were cultured in the absence (control cells) or in the presence of 100 μM of a cholesterol derivative, hemisuccinate of cholesterol. Cholesterol hemisuccinate-treatment alters cholesterol and lipid content of HepG2 and modulates membrane fluidity. Cholesterol hemisuccinate-treatment induces a decrease in insulin responsiveness and creates an 'insulin-resistant' state in these cells. Exposure to 100 μM of metformin resulted in a significant enhancement of insulin-stimulated lipogenesis in control and cholesterol hemisuccinate-treated cells. In control cells, metformin altered glycogenesis in a biphasic manner. In cholesterol hemisuccinate-treated cells, metformin inhibited basal glycogenesis but restored insulin-stimulated glycogenesis. Hence, to understand the mechanism of metformin action, we analyzed early steps in the insulin signaling pathway, including insulin receptor autophosphorylation, mitogen-activated-protein kinase and phosphatidylinositol 3-kinase activities, in both control and cholesterol hemisuccinate-treated cells. Overall, the results suggest that metformin may interact with the insulin receptor and/or a component involved in the early steps of insulin signal transduction. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)241-252
Number of pages12
JournalEuropean Journal of Pharmacology
Volume377
Issue number2-3
DOIs
StatePublished - Jul 21 1999
Externally publishedYes

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Metformin
Insulin Receptor
Hep G2 Cells
Hepatocellular Carcinoma
Cholesterol
Insulin
Biguanides
Phosphatidylinositol 3-Kinase
Lipogenesis
Membrane Fluidity
Mitogen-Activated Protein Kinases
cholesteryl succinate
Cultured Cells
Signal Transduction
Lipids
Cell Line

Keywords

  • Cholesterol
  • Insulin receptor
  • Metformin
  • Non-insulin dependent diabetes mellitus therapy

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Metformin modulates insulin receptor signaling in normal and cholesterol-treated human hepatoma cells (HepG2). / Meuillet, Emmanuelle; Wiernsperger, Nicolas; Mania-Farnell, Barbara; Hubert, Pierre; Cremel, Gerard.

In: European Journal of Pharmacology, Vol. 377, No. 2-3, 21.07.1999, p. 241-252.

Research output: Contribution to journalArticle

Meuillet, Emmanuelle ; Wiernsperger, Nicolas ; Mania-Farnell, Barbara ; Hubert, Pierre ; Cremel, Gerard. / Metformin modulates insulin receptor signaling in normal and cholesterol-treated human hepatoma cells (HepG2). In: European Journal of Pharmacology. 1999 ; Vol. 377, No. 2-3. pp. 241-252.
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