Induction of choleresis by immunosuppressant FK506 through stimulation of insulin-like growth factor-I production in the liver of rats

Eur J Pharmacol. 2001 May 4;419(1):99-105. doi: 10.1016/s0014-2999(01)00961-x.


FK506 (Tacrolimus) is an effective immunosuppressant currently used worldwide in organ transplantation. Based on our recent findings that insulin-like growth factor-I (IGF-I) is important for the stimulation of choleresis in vivo, in this study we investigated the effect of FK506 on bile flow and the plasma and hepatic levels of IGF-I in rats. Intravenous treatment of rats with FK506 resulted in a significant increase in bile flow, whereas cyclosporin A induced a significant decrease. A significant increase in plasma levels of IGF-I was observed in rats 30 min after a single intravenous administration of FK506. Oral treatment of rats with FK506 for 1 week also resulted in an increase in both plasma and hepatic levels of IGF-I. Overall, this study showed that FK506 treatment increased bile flow and also induced an increase in the plasma and hepatic levels of IGF-I in rats, suggesting that a stimulation of hepatic IGF-I production by FK506 may contribute to its choleretic profile.

MeSH terms

  • Animals
  • Bile / metabolism*
  • Cyclosporine / pharmacology
  • Hypophysectomy
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacology*
  • Insulin-Like Growth Factor I / chemistry
  • Insulin-Like Growth Factor I / metabolism*
  • Liver / chemistry
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Tacrolimus / administration & dosage
  • Tacrolimus / pharmacology*


  • Immunosuppressive Agents
  • Insulin-Like Growth Factor I
  • Cyclosporine
  • Tacrolimus