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Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats
  1. V Lorenzo-Zúñiga1,*,
  2. C M Rodríguez-Ortigosa2,*,
  3. R Bartolí1,
  4. M-L Martínez-Chantar2,
  5. L Martínez-Peralta2,
  6. A Pardo2,
  7. I Ojanguren3,
  8. J Quiroga2,
  9. R Planas1,
  10. J Prieto2
  1. 1Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
  2. 2Department of Medicine and Liver Unit, Clínica Universitaria, Medical School and Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain
  3. 3Department of Histology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain
  1. Correspondence to:
    Professor J Prieto
    Department of Medicine and Liver Unit, Clínica Universitaria and Centre for Applied Medical Research (CIMA), University of Navarra, 31080 Pamplona, Spain; jprieto{at}


Background and aims: In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats.

Methods: In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor α (TNF-α), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells.

Results: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-α expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes.

Conclusions: IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.

  • BDL, bile duct ligation
  • Colα1, procollagen α1(I)
  • GH, growth hormone
  • IBF, intestinal barrier function
  • IGF-I, insulin-like growth factor type I
  • PHE, portal hypertensive enteropathy
  • SBP, spontaneous bacterial peritonitis
  • TER, transepithelial electrical resistance
  • COX-2, cyclooxygenase 2
  • TNF-α, tumour necrosis factor α
  • LPS, lipopolysaccharide
  • CCl4, carbon tetrachloride
  • DMEM, Dulbecco’s modified Eagle’s medium
  • FBS, fetal bovine serum
  • RT-PCR, reverse transcription-polymerase chain reaction
  • bacterial peritonitis
  • hepatic fibrosis
  • intestinal barrier
  • rats

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  • Published online first 24 January 2006

  • * V Lorenzo-Zúñiga and C M Rodríguez-Ortigosa share equal first authorship.

  • Conflict of interest: None declared.

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