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 wa s to study Na+-dependent jejunal transport of amino acids (L-leucine, L-pro line, 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 w k to rats with CCl4-induced cirrhosis and saline was administered to health y control rats. Transport of amino acids was assessed in brush-border membr ane vesicles (BBMV) using C-14- or S-35-labeled amino acids, and the kineti c constants V-max and K-t were determined. Na+-independent uptake of L-leuc ine, 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 dimi nished in cirrhotic rats compared with both controls and IGF-I-treated cirr hotic 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 tra nsport of all four tested amino acids by BBMV is impaired in cirrhotic rats , and low doses of IGF-I can correct this defect.