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Author Yeom, Chul-gon ♦ Kim, Dong-il ♦ Park, Min-jung ♦ Choi, Joo-hee ♦ Jeong, Jieun ♦ Wi, Anjin ♦ Park, Whoashig ♦ Han, Ho-jae ♦ Park, Soo-hyun
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ARGININE ♦ CELL PROLIFERATION ♦ FASTING ♦ INSULIN ♦ KIDNEYS ♦ LIVER ♦ LIVER CELLS ♦ METHYLATION ♦ RATS ♦ SENSITIVITY ♦ SIGNALS
Abstract Previously, we reported that CARM1 undergoes ubiquitination-dependent degradation in renal podocytes. It was also reported that CARM1 is necessary for fasting-induced hepatic gluconeogenesis. Based on these reports, we hypothesized that treatment with insulin, a hormone typically present under the ‘fed’ condition, would inhibit gluconeogenesis via CARM1 degradation. HepG2 cells, AML-12 cells, and rat primary hepatocytes were treated with insulin to confirm CARM1 downregulation. Surprisingly, insulin treatment increased CARM1 expression in all cell types examined. Furthermore, treatment with insulin increased histone 3 methylation at arginine 17 and 26 in HepG2 cells. To elucidate the role of insulin-induced CARM1 upregulation, the HA-CARM1 plasmid was transfected into HepG2 cells. CARM1 overexpression did not increase the expression of lipogenic proteins generally increased by insulin signaling. Moreover, CARM1 knockdown did not influence insulin sensitivity. Insulin is known to facilitate hepatic proliferation. Like insulin, CARM1 overexpression increased CDK2 and CDK4 expression. In addition, CARM1 knockdown reduced the number of insulin-induced G2/M phase cells. Moreover, GFP-CARM1 overexpression increased the number of G2/M phase cells. Based on these results, we concluded that insulin-induced CARM1 upregulation facilitates hepatocyte proliferation. These observations indicate that CARM1 plays an important role in liver pathophysiology. - Highlights: • Insulin treatment increases CARM1 expression in hepatocytes. • CARM1 overexpression does not increase the expression of lipogenic proteins. • CARM1 knockdown does not influence insulin sensitivity. • Insulin-induced CARM1 upregulation facilitates hepatocyte proliferation.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-06-05
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 461
Issue Number 3


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