The immediate postnatal period is marked by extensive growth and maturation of the gastrointestinal (GI) tract. This growth is potentiated by ingestion of colostrum and is presumably due to colostral growth factors (GFs). Roles for epidermal growth factor (EGF) and insulin in GI development have received considerable attention, however a role for the insulin-like growth factors (IGF-I and IGF-II) has not been well studied. IGFs are growth hormone-dependent peptides with metabolic and anabolic actions in vivo and in vitro. They circulate associated with binding proteins (IGFBPs) which prolong their half-lives and mediate their availability to target tissues. The objective of this research is to investigate the role IGF-I and -II and IGFBPs in neonatal GI development. Intestinal development of the small-for-gestational-age (SGA) or low birth weight (LBW) infant is of particular clinical relevance. With improved survival of LBW infants, attention is now focusing upon their nutritional support. However, many LBW infants demonstrate poor tolerance to enteral feedings, related in part to inadequate mechanical and digestive function of their GI tracts. LBW infants are often given total parenteral nutrition (TPN) when enteral intolerance exceeds 2 to 5 days postpartum. However, extended use of TPN may cause gut atrophy, further compromising the GI tract of the LBW infant. The proposed research will combine in vitro studies of intestinal explants with integrated whole animal in vivo studies. In vivo studies will employ the colostrum-deprived piglet model and will involve both appropriate-for- gestational-age (AGA) and SGA piglets.
The specific aims of this research are: 1) to determine the stability of IGFs and IGFBPs to in vitro digestion with gastric and intestinal secretions from neonatal and adult pigs; 2) to investigate the action of IGFs alone and in combination with other milk GFs on DNA synthesis, digestive enzyme activity, and IGF and IGFBP synthesis by pig intestinal explants in vitro; 3) to study the effect of oral ingestion of IGF-I or -II supplemental milk replacer on piglet GI development and function; and 4) to test the efficacy of enteral IGF-I administration in stimulating GI development of the SGA piglet on TPN. The knowledge gained by this research will provide better understanding of the role of IGFs in the developing neonate and will provide clinically relevant data for further studies in premature infants.
