2. Academic Validation
  3. AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells

AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells

  • Biochem Biophys Res Commun. 2005 Mar 11;328(2):449-54. doi: 10.1016/j.bbrc.2005.01.004.
Kazuhiko Nakamaru 1,  Kazuya Matsumoto,  Tetsuya Taguchi,  Mihoshi Suefuji,  Yusuke Murata,  Motoyuki Igata,  Junji Kawashima,  Tatsuya Kondo,  Hiroyuki Motoshima,  Kaku Tsuruzoe,  Nobuhiro Miyamura,  Tetsushi Toyonaga,  Eiichi Araki
Affiliations

Affiliation

  • 1 Department of Metabolic Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
PMID: 15694368 DOI: 10.1016/j.bbrc.2005.01.004
Abstract

The liver is one of the major target organs of Insulin in which the expression of Insulin Receptor is abundant. We analyzed the effect of AICAR, an AMPK Activator, on the expression of Insulin Receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48 h significantly decreased the expression of the Insulin Receptor protein in a dose-dependent manner, however, this same effect of AICAR was not observed in either 3T3-L1 adipocytes or CHO cells. The expression of Insulin Receptor mRNA also decreased after AICAR treatment. In addition, the transcriptional activity of the Insulin Receptor gene promoter investigated with a luciferase assay was down-regulated by AICAR treatment. Dipyridamole, an adenosine transporter inhibitor, and 5'-amino-5'-deoxyadenosine, an Adenosine Kinase Inhibitor, blocked the effect of AICAR on the down-regulation of the Insulin Receptor protein, mRNA, and promoter activity. Our findings suggest, for the first time, that AMPK activation could reduce the expression of Insulin Receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific.

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