EPIDERMAL GROWTH FACTOR, OBESITY & INSULIN RESISTANCE

该项目的长期目标是确定环境 发育期间的暴露有助于获得肥胖或 胰岛素抵抗特征。如果成功的话，也许有可能 制定早期干预策略， 至少要预防这些疾病的发生。 建议的研究 本申请涉及表皮生长因子（EGF）的作用， 在胎儿发育过程中， 动物变得肥胖或胰岛素抵抗的易感性， 成年人了 在子宫内和新生儿早期，EGF主要是 母性起源 在怀孕的动物中，EGF依赖于 合成和外分泌的颌下腺，而在 新生儿期EGF通过乳腺合成传递给幼崽 组织和分泌物进入乳汁。 在这两种情况下，EGF 被完整吸收，尽管其全身效应尚未明确定义。 EGF在胰岛素抵抗中的作用 流行病学研究表明， 胎儿生长受损成人和动物胰岛素抵抗 研究表明在EGF条件下胎儿生长迟缓 怀孕期间缺乏。 EGF含量的增加， 牛奶与动物的高度倾向性有关， 积累脂肪并变得肥胖。本项目的研究将审查 环境因素对下颌骨下表皮生长因子分泌的影响 在怀孕期间的腺体，并确定是否减少EGF释放导致 导致胎儿生长减慢，最终导致成人胰岛素抵抗 动物 研究还将研究牛奶中EGF的作用， 促进新生动物的脂肪组织发育。一个主要 这项建议的原则是，早期生活事件， 动物变得肥胖不同于那些促进随后的 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.