Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I.
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 CCl(4)-induced cirrhosis and saline was administered to healthy control rats. Transport of amino acids was assessed in brush-border membrane vesicles (BBMV) using (14)C- or (35)S-labeled amino acids, and the kinetic constants V(max) and K(t) 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 V(max) and K(t), whereas untreated cirrhotic rats had reduced V(max) and increased K(t) 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.
Department of Human Physiology, Liver Unit, University of Navarra, Pamplona, Spain.
M
M
Pascual
I
I
Castilla-Cortazar
E
E
Urdaneta
J
J
Quiroga
M
M
Garcia
A
A
Picardi
J
J
Prieto
D000596:Amino Acids / Q000493:pharmacokinetics*; D000818:Animals; D003545:Cysteine / Q000493:pharmacokinetics; D018698:Glutamic Acid / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects* / Q000502:physiology*; D007583:Jejunum / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000493:pharmacokinetics; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D008286:Malabsorption Syndromes / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009748:Nutrition Disorders / Q000188:drug therapy / Q000503:physiopathology; D011392:Proline / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D000596:Amino Acids; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D011392:Proline; D007930:Leucine; D003545:Cysteine