INSULIN-LIKE GROWTH FACTORS IN INTESTINAL DEVELOPMENT

肠道发育中的胰岛素样生长因子

• 批准号: 2201694
• 负责人: SHARON Marie DONOVAN
• 金额: $ 15.01万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2201694
• 关键词: DNA replication; colostrums; developmental nutrition; dietary supplements; gastrointestinal system; gestational age; growth /development; growth factor; hormone binding protein; infant animal; insulinlike factor; mature animal; milk; nucleic acid probes; nutrition related tag; parenteral feedings; premature infant animal; radioimmunoassay; radiotracer; recombinant DNA; swine; tissue /cell culture; western blottings

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.

产后直接的时期以广泛的增长和成熟为标志 胃肠道（GI）。 这种增长受到 摄入初乳，大概是由于归结于造影剂的生长因子 （GFS）。 表皮生长因子（EGF）和胰岛素在GI中的作用 发展受到了很大的关注，但是 胰岛素样生长因子（IGF-I和IGF-II）尚未得到很好的研究。 IGF是具有代谢和合成代谢的生长激素依赖性肽 在体内和体外作用。 它们与结合有关 蛋白质（IGFBP）延长其半衰期并调解其 靶组织的可用性。 这项研究的目的是 研究IGF -I和-II和IGFBP在新生儿GI发育中的作用。 小胎龄（SGA）或低出生的肠发展 体重（LBW）婴儿特别临床相关。 有了改进 LBW婴儿的生存，现在注意力集中在其营养上 支持。 但是，许多LBW婴儿表现出对肠内的耐受性不佳 喂食，部分与机械和消化功能不足有关 他们的胃肠道。 LBW婴儿经常得到总肠胃外营养 （TPN）当肠内不耐受超过产后2至5天。 然而， TPN的扩展使用可能会导致肠道萎缩，进一步损害GI LBW婴儿的道。 拟议的研究将结合肠外植物的体外研究 随着整个动物的体内研究。 体内研究将采用 剥夺仔猪模型，将涉及适当的合适 妊娠年龄（AGA）和SGA小猪。 这项研究的具体目的 是：1）确定IGF和IGFBPS在体外的稳定性 新生儿和成人的胃和肠道分泌物消化 猪； 2）单独研究IGF的作用并与 其他有关DNA合成，消化酶活性和IGF和IGF和IGF和的牛奶GFS 猪肠外植物在体外由猪肠外植体合成； 3）研究效果 在小猪GI上口服IGF -I或-II补充牛奶替代品 发展和功能； 4）测试肠内IGF-I的功效 在TPN上刺激SGA Piglet的胃肠道发育。 这 这项研究获得的知识将更好地理解 IGF在发育中的新生儿中的作用，将提供临床相关的 用于进一步研究过早婴儿的数据。