Insulin-like growth factor-I (IGF-I) stimulates regrowth of the damaged intestine in rats, when administered following, but not concurrent with, methotrexate

Growth Factors. 1998;15(4):279-92. doi: 10.3109/08977199809017483.


Background: We tested the ability of insulin-like growth factor-I (IGF-I) to reduce damage to the intestinal mucosa (mucositis) in rats injected with methotrexate. IGF-I was infused concurrent with methotrexate administration and compared to IGF-I administered following the withdrawal of methotrexate.

Methods: Rats were injected with methotrexate at the start of days 1, 2 and 3. IGF-I was infused for 5 days, commencing at the start of day 1 [concurrent administration] or at the start of day 4 [post-methotrexate administration].

Results: IGF-I administered coincident with methotrexate failed to restore mucosal integrity to the damaged small intestine. IGF-I administered post methotrexate stimulated regrowth of the damaged intestine, particularly the ileum, with 22%, 32% and 29% increases in small intestinal weight, ileal villus height and ileal crypt depth respectively.

Conclusions: Following intestinal damage of methotrexate, IGF-I primarily induced growth of the distal small intestine. The ineffectiveness of concurrently administered IGF-I may have represented an IGF-I induced recruitment of proliferating epithelial cells to the anti-proliferative effects of methotrexate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage*
  • DNA / analysis
  • Insulin-Like Growth Factor Binding Proteins / blood
  • Insulin-Like Growth Factor I / administration & dosage*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / physiology*
  • Male
  • Methotrexate / administration & dosage*
  • Organ Size
  • Proteins / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration / physiology*
  • Sucrase / metabolism


  • Antimetabolites, Antineoplastic
  • Insulin-Like Growth Factor Binding Proteins
  • Proteins
  • Insulin-Like Growth Factor I
  • DNA
  • Sucrase
  • Methotrexate