title: Jejunal microvilli atrophy and reduced nutrient transport in rats with advanced liver cirrhosis: improvement by Insulin-like Growth Factor I.
abstract: BACKGROUND
  Previous results have shown that in rats with non-ascitic cirrhosis there is an altered transport of sugars and amino acids associated with elongated microvilli. These alterations returned to normal with the administration of Insulin-Like Growth Factor-I (IGF-I). The aims of this study were to explore the evolution of these alterations and analyse the effect of IGF-I in rats with advanced cirrhosis and ascites. Thus, jejunal structure and nutrient transport (D-galactose, L-leucine, L-proline, L-glutamic acid and L-cystine) were studied in rats with ascitic cirrhosis.
  
  
  METHODS
  Advanced cirrhosis was induced by CCl4 inhalation and Phenobarbital administration for 30 weeks. Cirrhotic animals were divided into two groups which received IGF-I or saline during two weeks. Control group was studied in parallel. Jejunal microvilli were studied by electron microscopy. Nutrient transport was assessed in brush border membrane vesicles using 14C or 35S-labelled subtracts in the three experimental groups.
  
  
  RESULTS
  Intestinal active Na+-dependent transport was significantly reduced in untreated cirrhotic rats. Kinetic studies showed a decreased Vmax and a reduced affinity for sugar and four amino acids transporters (expressed as an increased Kt) in the brush border membrane vesicles from untreated cirrhotic rats as compared with controls. Both parameters were normalised in the IGF-I-treated cirrhotic group. Electron microscopy showed elongation and fusion of microvilli with degenerative membrane lesions and/or notable atrophy.
  
  
  CONCLUSIONS
  The initial microvilli elongation reported in non ascitic cirrhosis develops into atrophy in rats with advanced cirrhosis and nutrient transports (monosaccharides and amino acids) are progressively reduced. Both morphological and functional alterations improved significantly with low doses of IGF-I.
authors.affiliation: Department of Physiology, Clínica Universitaria, University of Navarra, Pamplona, Spain. iccortazar@uma.es
authors.forename: Inma
authors.initials: I
authors.lastname: Castilla-Cortázar
authors.forename: María
authors.initials: M
authors.lastname: Pascual
authors.forename: Elena
authors.initials: E
authors.lastname: Urdaneta
authors.forename: Javier
authors.initials: J
authors.lastname: Pardo
authors.forename: Juan Enrique
authors.initials: JE
authors.lastname: Puche
authors.forename: Bárbara
authors.initials: B
authors.lastname: Vivas
authors.forename: Amelia
authors.initials: A
authors.lastname: Díaz-Casares
authors.forename: María
authors.initials: M
authors.lastname: García
authors.forename: Matías
authors.initials: M
authors.lastname: Díaz-Sánchez
authors.forename: Isabel
authors.initials: I
authors.lastname: Varela-Nieto
authors.forename: Alberto
authors.initials: A
authors.lastname: Castilla
authors.forename: Salvador
authors.initials: S
authors.lastname: González-Barón
mesh_terms: D000596:Amino Acids / Q000493:pharmacokinetics; D000818:Animals; D001284:Atrophy; D001692:Biological Transport; D002251:Carbon Tetrachloride; D005690:Galactose / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism* / Q000473:pathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008871:Microvilli / Q000378:metabolism* / Q000648:ultrastructure*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000596:Amino Acids; D007334:Insulin-Like Growth Factor I; D002251:Carbon Tetrachloride; D005690:Galactose