Mechanistic evaluation of the insulin response in H4IIE hepatoma cells: new endpoints for toxicity testing?
This study was designed to evaluate if the rat H4IIE hepatoma cell line is a physiologically relevant model to study hepatic insulin responses to hint at its prospective application in pollutant-related insulin resistance research. DNA microarray analysis, real-time PCR and flow cytometric cell cycle analysis were used to assess the relevance of the insulin response in H4IIE cells. Insulin dose dependently stimulated H4IIE growth and time dependently altered the expression of the known insulin responsive genes: Fasn, Pck1 and Irs2. Microarray analysis performed on cells exposed to insulin (100nM) for 6h and 24h showed that genes related to carbohydrate and lipid metabolism were most profoundly afflicted, in accordance with in vivo hepatic insulin action. Since changes in carbohydrate and lipid metabolism are pivotal in the pathogenesis of insulin resistance, the presence of a physiological relevant insulin response in H4IIE cells pleads for further testing of its potential use in research on pollutant-driven insulin resistance.
Department of Biology, Laboratory of Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. tine.hectors@ua.ac.be
Tine L M
TL
Hectors
Caroline
C
Vanparys
Anna
A
Pereira-Fernandes
Dries
D
Knapen
Ronny
R
Blust
D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005434:Flow Cytometry; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects