Our objective was to determine the potentially anabolic effects of orally administered recombinant human insulin-link growth factor I (rhIGF-I)on small intestinal growth in formula-fed neonatal pigs. Unsuckled neonatal pigs received formula or formula containing added rhIGF-I (3.5 mg.kg-1.day-1) from birth to 4 days of age. Pigs in both groups were fed 30 ml/kg formula every 2 h on day 1 and then every 4 h on days 2-4, and blood was sampled daily. Oral administration of rhIGF-I to formula-fed neonatal pigs increased small intestinal weight, protein, and DNA content,but not length. Jejunal and ileal villus height, but not crypt depth or muscularis thickness, also were increased by oral rhIGF-I administration. Neither the circulating concentration of IGF-I nor the IGF-binding proteins differed between control and oral rhIGF-treated pigs, suggesting that the absorption of orally administered rhIGF-I from the intestinal lumen into the peripheral circulation was limited. Our results demonstrate that oral administration of rhIGF-I during the first 4 days after birth significantly increased small intestinal mucosal growth in formula-fed neonatal pigs. These results suggest that oral administration of rhIGF-I may be a viable therapeutic approach to enhance intestinal growth in neonates.
Despite significant advances in our understanding of the roles of the cytoskeleton and matrix receptors in cell locomotion, derived largely from in vitro studies on the movement of epithelial cell sheets and isolated cells, the mechanism of epithelial cell migration in the adult intestine remains an enigma. The primary function of the epithelial cell cytoskeleton seems to be in the maintenance of the apical region of the epithelium facing the gut lumen. There we find the brush border, with its associated enzymes, and the intercellular adhesion complexes that give the epithelium its cohesiveness and its barrier function. Curiously, there is little in the way of an organized cytoskeleton in the basal region of the epithelium adjacent to the basement membrane on which the epithelium is presumed to migrate. In this short review, I focus on what is known about epithelial migration from our understanding of the structure of the epithelium and from studies on wound healing, and indicate some avenues for future study.
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