Troglitazone stimulates IGF-binding protein-1 by a PPAR gamma-independent mechanism

Biochem Biophys Res Commun. 2003 Apr 4;303(2):693-9. doi: 10.1016/s0006-291x(03)00403-0.

Abstract

IGFBP-1 modulates IGF availability for glucose homeostasis and it may also play a paracrine role in hepatocyte survival. IGFBP-1 is inhibited transcriptionally by insulin and is also regulated by a number of pathways that influence hepatic insulin sensitivity. The effect of the thiazolidinedione troglitazone on IGFBP-1 production was studied in HepG2 human hepatoma cells, which were found to express PPAR alpha, PPAR gamma, and PXR. Troglitazone stimulated IGFBP-1 mRNA expression 2-fold within 3h of exposure (P<0.001) and stimulated secretion up to 3-fold over a narrow dose range within 24h (P<0.001). This effect was mimicked by the PXR ligands clotrimazole and phenobarbital, but not by Wy14,643 or rosiglitazone, which are ligands for PPAR alpha and -gamma, respectively. We conclude that the effect of troglitazone on IGFBP-1 production by HepG2 cells is independent of PPAR and may involve PXR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular
  • Chromans / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin-Like Growth Factor Binding Protein 1 / genetics*
  • Kinetics
  • Liver Neoplasms
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Rosiglitazone
  • Thiazoles / pharmacology*
  • Thiazolidinediones*
  • Transcription Factors / physiology*
  • Transcription, Genetic / drug effects
  • Troglitazone
  • Tumor Cells, Cultured

Substances

  • Chromans
  • Hypoglycemic Agents
  • Insulin-Like Growth Factor Binding Protein 1
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Rosiglitazone
  • Troglitazone