Insulin signaling and glucose metabolism in different hepatoma cell lines deviate from hepatocyte physiology toward a convergent aberrant phenotype.

Scientific Reports
Angela MolinaroGiovanni Solinas

Abstract

Hepatoma cell lines are widely used to model the hepatocyte for insulin signaling and fatty liver disease. However, a direct comparison of insulin action in primary hepatocytes and in hepatoma cell lines is needed to validate this model and to better understand liver cancer. Here we have investigated insulin signaling, gluconeogenic gene expression, glucose production, and fatty acid synthase abundance in primary hepatocytes and in HepG2, Hepa 1-6, and McARH7777 hepatoma cell lines. Differences in the electrophoretic profiles of protein extracts from human and mouse primary hepatocytes and the hepatoma cells lines are shown. Compared to primary hepatocytes, hepatoma cells showed high basal phosphorylation of AKT at Thr 308 and constitutively activated RAS-MAPK signaling, which were resistant to the dominant negative Ras mutant H-Ras17N. Hepatoma cell lines also showed defective expression of gluconeogenic enzymes, insulin unresponsive GSK phosphorylation, and marginal glucose production. Hepatoma cells also showed lower protein levels of fatty acid synthase and a largely distinct protein electrophoresis profile from hepatocytes but similar between different hepatoma lines. We conclude that hepatoma cell lines do not accurately ...Continue Reading

References

Mar 26, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Cliff RoweNeil A Hanley
May 15, 2015·Molecular Metabolism·Giovanni SolinasAbdul G Dulloo
Apr 19, 2017·Trends in Endocrinology and Metabolism : TEM·Paul M TitchenellMorris J Birnbaum
Jul 14, 2017·Clinical Diabetes and Endocrinology·Paul Z Zimmet
Sep 5, 2017·Cell Metabolism·Varman T Samuel, Gerald I Shulman
Aug 2, 2018·Physiological Reviews·Max C Petersen, Gerald I Shulman
Jan 29, 2019·The Journal of Clinical Investigation·Wei WangFeng Yang
Jan 30, 2019·American Journal of Physiology. Endocrinology and Metabolism·Shilpa R NagarajanAndrew J Hoy

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Citations

Jul 10, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Yuandi DongHaiyang Wang

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Methods Mentioned

BETA
electrophoresis
electrophoretic profile

Software Mentioned

GraphPad Prism
BioRad Image Lab

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