Posttranslational processing of SREBP-1 in rat hepatocytes is regulated by insulin and cAMP

Biochem Biophys Res Commun. 2005 Jun 24;332(1):174-80. doi: 10.1016/j.bbrc.2005.04.112.

Abstract

Insulin and cAMP have opposing effects on de novo fatty acid synthesis in liver and in cultured hepatocytes mediated by sterol-regulatory element binding protein (SREBP). To determine whether these agents regulate the cleavage of full-length SREBP to generate the transcriptionally active N-terminal fragment (nSREBP) in primary rat hepatocytes, an adenoviral vector (Ad-SREBP-1a) was constructed to constitutively express full-length SREBP-1a. Insulin increased, and dibutyryl (db)-cAMP inhibited, generation of nSREBP-1a from its full-length precursor. Insulin stimulated processing of SREBP-1a within 1h, and the effect was sustained for at least 24h. The initial stimulation of SREBP processing by insulin preceded measurable reduction in Insig-2 mRNA levels. Rat hepatocytes were also infected with an adenovirus expressing the nuclear form of SREBP-1c (Ad-nSREBP-1c). Insulin increased the half-life of constitutively expressed nSREBP-1c, and this effect of insulin was also inhibited by db-cAMP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Proteins / metabolism*
  • Cells, Cultured
  • Cyclic AMP / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Insulin / metabolism*
  • Insulin / pharmacology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Membrane Proteins / metabolism*
  • Protein Processing, Post-Translational / drug effects
  • Protein Processing, Post-Translational / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors / metabolism*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • DNA-Binding Proteins
  • INSIG2 protein, human
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Srebf1 protein, rat
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Cyclic AMP