Vol. 279, Issue 2, G319-G324, August 2000
Altered intestinal transport of amino acids in cirrhotic rats:
the effect of insulin-like growth factor-I
Maria
Pascual1,
Inma
Castilla-Cortazar1,2,
Elena
Urdaneta1,
Jorge
Quiroga3,
Maria
Garcia1,2,
Antonio
Picardi1,4, and
Jesus
Prieto2
Departments of 1 Human Physiology and 3 Internal
Medicine, Liver Unit, University of Navarra, 31008 Pamplona;
2 Department of Physiology, School of Medicine, University of
Málaga, 29008 Málaga, Spain; and 4 Libero Istituto
Universitario, Campus Bio-medico, 00155 Rome, Italy.
The intestine is an
important target organ for insulin-like growth factor-I (IGF-I), an
anabolic hormone synthesized in the liver upon growth hormone (GH)
stimulation. Levels of IGF-I are reduced in cirrhosis, and altered
GH/IGF-I axis may contribute to malnutrition in cirrhotic patients. Our
aim was to study Na+-dependent jejunal transport of amino
acids (L-leucine, L-proline, L-glutamic acid, and L-cysteine) in cirrhotic
rats and to analyze the effect of IGF-I on this function. IGF-I or
saline was administered for 2 wk to rats with CCl4-induced
cirrhosis and saline was administered to healthy control rats.
Transport of amino acids was assessed in brush-border membrane vesicles
(BBMV) using 14C- or 35S-labeled amino acids,
and the kinetic constants Vmax and
Kt were determined. Na+-independent
uptake of L-leucine, L-proline,
L-glutamic acid, and L-cysteine by BBMV was
similar in all groups. Na+-dependent uptake of all four
amino acids was significantly diminished in cirrhotic rats compared
with both controls and IGF-I-treated cirrhotic rats. The latter two
groups exhibited similar Vmax and Kt, whereas untreated cirrhotic rats had reduced
Vmax and increased Kt
compared with normal controls and IGF-I-treated cirrhotic animals. In
conclusion, the transport of all four tested amino acids by BBMV is
impaired in cirrhotic rats, and low doses of IGF-I can correct this defect.
liver; malabsorption; malnutrition; intestinal absorption
