TISSUE-SPECIFIC EFFECTS OF CHRONIC DIETARY-PROTEIN RESTRICTION AND GASTROSTOMY ON THE INSULIN-LIKE GROWTH-FACTOR-I PATHWAY IN THE LIVER ANDCOLON OF ADULT-RATS

Dietary protein restriction decreases plasma concentrations of insulin -like growth factor-I (IGF-I) and reduces IGF-I mRNA levels in the liv er, In addition to the actions of systemic IGF-I, locally produced IGF -I is thought to mediate autocrine and paracrine growth effects in the colon, The objectives of the present study were to investigate the IG F-I pathway in the colon and liver of adult rats under conditions of d ietary protein restriction, surgical stress, and dietary protein reple tion. Two groups of rats were placed on either a 20% or 2% casein diet for 19 days, Two additional groups of rats underwent gastrostomy afte r a 2% casein diet for 2 weeks, and then were either kept on the 2% ca sein diet or changed to a 20% casein diet until day 19. Dietary protei n restriction reduced plasma concentrations of IGF-I and IGF-binding p roteins (IGFBPs) and hepatic IGF-I mRNA content, while increasing colo nic IGF-I receptor mRNA, Gastrostomy in protein-depleted animals had n o effect on hepatic IGF-I mRNA, but led to a marked increase in coloni c IGF-I mRNA levels. Dietary protein repletion resulted in a decrease in colonic IGF-I receptor mRNA. The distinct effects of dietary protei n depletion and operative stress on the IGF pathway in the colon as co mpared with the liver may serve to maintain the level of IGF-I signali ng in the colon by autocrine or paracrine mechanisms under these condi tions. Copyright (C) 1997 by W.B. Saunders Company.