Identification of insulin-responsive regions in the HMG-CoA reductase promoter

Biochem Biophys Res Commun. 2004 Jun 11;318(4):814-8. doi: 10.1016/j.bbrc.2004.04.105.


An insulin-responsive line of rat hepatoma cells, H4IIE, was used to investigate the basis for insulin's transcriptional regulation of HMG-CoA reductase. Insulin addition to the media of these cells resulted in at least a 10-fold increase in levels of HMG-CoA reductase protein. Adding insulin to H4IIE cells transfected with pHMGR1 (containing the proximal reductase promoter from -270 to +20 ligated to luciferase) caused greater than 10-fold increases in luciferase activity. Transfections carried out with a series of deletion constructs identified insulin responsive regions between -203 and -130 (contains the SRE sequence) and between -85 and -105 (contains a CRE sequence). Mutation of the SRE in the -203 to -130 sequence did not decrease activation by insulin. In contrast, mutation of the C at -90 of the CRE completely eliminated the insulin response. The data suggest that insulin's activation of HMG-CoA reductase involves the CRE in the -85 to -105 region and the -203 to -130 region of the promoter exclusive of the SRE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cyclic AMP / metabolism
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Genes, Reporter
  • Hydroxymethylglutaryl CoA Reductases / biosynthesis
  • Hydroxymethylglutaryl CoA Reductases / genetics*
  • Immunoblotting
  • Insulin / pharmacology*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Mutation
  • Promoter Regions, Genetic / drug effects*
  • Promoter Regions, Genetic / genetics
  • Rats
  • Response Elements / genetics
  • Transfection


  • Insulin
  • Cyclic AMP
  • Hydroxymethylglutaryl CoA Reductases
  • Luciferases