Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line

Metabolism: Clinical and Experimental
Kazue HonmaToshinao Goda

Abstract

Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes.

References

May 4, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sanjay B JadhaoSanjay B Jadaho
Oct 13, 2006·Molecular and Cellular Biology·Christopher R VakocGerd A Blobel
May 14, 2009·Journal of Nutritional Science and Vitaminology·Naoko SakuraiToshinao Goda
Nov 27, 2010·Biochemical and Biophysical Research Communications·Hiroshi OisoEiichi Araki
Mar 24, 2012·Current Opinion in Genetics & Development·Oliver J Rando
Apr 3, 2014·Comprehensive Physiology·Liangyou Rui

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