EPIDERMAL GROWTH FACTOR, OBESITY & INSULIN RESISTANCE

这个项目的长期目标是确定如何保护环境 发育过程中的暴露会导致肥胖或 成人的胰岛素抵抗特征。如果成功，或许有可能 制定早期干预策略，以预防或控制 至少要预防这些疾病的发生。建议进行的研究 这项应用解决了表皮生长因子(EGF)的作用 安氏杆菌宫内和出生后分泌物的发育 动物对肥胖或胰岛素抵抗的易感性 成年人。在宫内和新生儿早期，EGF主要是 母系血统。在怀孕的动物中，循环中的EGF依赖于 颌下腺的合成和外分泌，而在 新生儿期EGF通过乳房合成传递给幼崽 组织和分泌物进入乳汁。在这两种情况下，摄入的EGF 被原封不动地吸收，尽管其系统性影响没有明确定义。 表皮生长因子在胰岛素抵抗发病中的潜在重要性 是根据流行病学研究的观察得出的结论 胎儿生长受损的成人和动物的胰岛素抵抗 EGF条件下胎儿生长迟缓的研究 孕期缺乏症。相比之下，EGF含量的提升在 牛奶与动物更倾向于 积聚脂肪，变得肥胖。这个项目中的研究将检查 影响颌下腺分泌EGF的环境因素 并确定EGF释放的减少是否会导致 导致胎儿生长发育减退，最终导致成人胰岛素抵抗 动物。研究还将检查乳源性EGF在 促进新生动物脂肪组织的发育。一位校长 这项提议的宗旨是，早期生活事件容易发生 动物变得肥胖不同于那些促进随后肥胖的动物 胰岛素抵抗的发展。

The long-term goal of this project is to determine how environmental exposures during development contribute to acquisition of obese or insulin resistant traits in the adult. If successful, it may be possible to devise strategies for early intervention which might prevent or at least forestall the onset of these disorders. The studies proposed in this application address the role of epidermal growth factor (EGF) secretion during intrauterine and postnatal life in development of an animal's susceptibility to become obese or insulin resistant as an adult. During intrauterine and early neonatal life EGF is largely of maternal origin. In pregnant animals circulating EGF is dependent upon synthesis and exocrine secretion from submandibular gland, while in the neonatal period EGF delivery to pups occurs via synthesis in mammary tissue and secretion into milk. In both circumstances, the ingested EGF is absorbed intact, though its systemic effects are not clearly defined. The potential importance of EGF for development in insulin resistance is suggested by observations from epidemiological studies linking insulin resistance in adults with impaired fetal growth and from animal studies demonstrating fetal growth retardation in conditions of EGF deficiency during pregnancy. In contrast, elevations of EGF content in milk as associated with a heightened propensity for animals to accumulate fat and become obese. Studies in this project will examine the environmental factors which influence EGF secretion by submandibular gland during pregnancy and determine if reduction in EGF release lead to decreased fetal growth and ultimately to insulin resistance in adult animals. Studies will also examine the role of milk-borne EGF in fostering adipose tissue development in neonatal animals. A principal tenet of this proposal is that early life events which predispose animals to become obese differ from those which promote subsequent development in insulin resistance.