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Metabolism. 2017 Jun;71:118-124. doi: 10.1016/j.metabol.2017.03.009. Epub 2017 Mar 23.

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

Author information

1
Laboratory of Nutritional Physiology, Department of Nutrition and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.
2
Laboratory of Nutritional Physiology, Department of Nutrition and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan; Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.
3
Laboratory of Nutritional Physiology, Department of Nutrition and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan. Electronic address: gouda@u-shizuoka-ken.ac.jp.

Abstract

OBJECTIVES:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Gluconeogenesis; HepG2; Histone acetylation; Insulin

PMID:
28521864
DOI:
10.1016/j.metabol.2017.03.009
[Indexed for MEDLINE]

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