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
Dec 15, 2010·Gastroenterology·Diego F CalvisiMatthias Evert
Sep 11, 2012·Diabetes·Helena MarcelinoAbdul G Dulloo
Mar 26, 2013·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Cliff RoweNeil A Hanley
Oct 24, 2013·Nature Communications·Ruihua MaBo Huang
May 15, 2015·Molecular Metabolism·Giovanni SolinasAbdul G Dulloo
Jun 6, 2015·BMC Medical Genomics·Bin ChenAtul J Butte
Jan 31, 2016·Journal of Proteomics·Jacek R WiśniewskiPer Artursson
Mar 30, 2017·JCI Insight·Dale S EdgertonAlan D Cherrington
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
Jun 11, 2018·Journal of Hepatology·Chris EstesHomie Razavi
Aug 2, 2018·Physiological Reviews·Max C Petersen, Gerald I Shulman
Oct 26, 2018·Open Biology·Stephanie SefriedSabine S Eckstein
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
Apr 16, 2019·Cell Metabolism·Angela MolinaroGiovanni Solinas