Altered intestinal transport of amino acids in cirrhotic rats: the effect of insulin-like growth factor-I

Abstract

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.

Effects of IGF-I treatment on osteopenia in rats with advanced liver cirrhosis

“…Reduced levels of sexual hormones and malabsorption have been reported as factors involved in the pathogenesis of osteopenia. In fact, cirrhotic animals included in these series had reduced levels of testosterone (7) and sugar and amino acid malabsorption (8,26). These alterations also improved with low doses of IGF-I (7,8,26).…”

Nutritional and Clinical Evaluation of a Modified Soy Protein with Covalently Bound Branched-Chain Amino Acids in Cirrhotic Sprague-Dawley Rats

“…Although the gut works well in cirrhotic patients, the intestinal transport of amino acids (as well as that of other nutrients) is diminished [29]. Therefore, a high proportion of ingested free amino acids, such as those from the diet H, are lost, while small peptides are absorbed along the intestine [13].…”

Gastrointestinal Dysfunction in Chronic Liver Disease

“…Whilst intestinal dysmotility has been associated with SIBO in noncirrhotic patients and experimental models of cirrhosis [77][78][79], the data relating the impact of small bowel motor abnormalities on SIBO are more controversial in patients with cirrhosis. Chesta et al [22] found no difference in the motility pattern in cirrhotic patients with or without SIBO, and treatment of bacterial overgrowth with tetracycline did not significantly alter small intestinal motility apart from reducing the time in phase 2 that was occupied by multiple-clustered contractions.…”

“…Malabsorption may also contribute to the malnutrition in liver cirrhosis. In experimental models of cirrhosis, intestinal absorption of carbohydrate, fat and protein have been shown to be significantly reduced [16,17,77]. Although fat malabsorption has been reported to occur in up to two-thirds of patients with cirrhosis [59], the absorption of carbohydrate does not appear to be reduced in these patients, using combined sugar probes (D-Xylose/3-O-methyl-D-glucose and rhamnose/3-OMG) [13,91].…”