Negative regulation of adiponectin receptor 1 promoter by insulin via a repressive nuclear inhibitory protein element

FEBS Lett. 2008 Oct 15;582(23-24):3401-7. doi: 10.1016/j.febslet.2008.08.037. Epub 2008 Sep 19.

Abstract

Adiponectin is an adipose-derived hormone that has anti-diabetic and anti-atherogenic effects through interaction with adiponectin receptors AdipoR1 and AdipoR2. We analyzed the transcriptional regulation of AdipoR1 by insulin. Insulin repressed the promoter activity of AdipoR1 in C2C12 myoblasts via PI3K and Foxo1. Deletion studies demonstrated the presence of a putative insulin-responsive region which is composed of a nuclear inhibitory protein (NIP) binding element. Mutation of the NIP element abrogated the negative regulation of AdipoR1 promoter by insulin. Insulin treatment could induce formation of a protein complex that bound the NIP element. Collectively, our data suggest that a repressive NIP element is involved in the negative regulation of AdipoR1 promoter by insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DNA Mutational Analysis
  • Down-Regulation
  • Electrophoretic Mobility Shift Assay
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation*
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Mice
  • Myoblasts / drug effects
  • Myoblasts / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Receptors, Adiponectin / genetics*
  • Response Elements* / drug effects
  • Sequence Deletion

Substances

  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • Insulin
  • Receptors, Adiponectin
  • adiponectin receptor 1, mouse
  • Phosphatidylinositol 3-Kinases