Influence of nutrients on islet development and function

描述(申请人提供)：宫内发育迟缓(IUGR) 增加围产期发病率和死亡率的相对风险，以及 流行病学证据表明有成人发病的倾向 与胎儿代谢异常有关。胰腺的微扰 宫内发育迟缓可能导致不适当的β细胞个体发育 导致大量不能处理新陈代谢的β细胞 压力。这个项目的长期目标是了解机制 潜在的胰腺发育和/或功能异常导致 胎儿宫内发育迟缓婴儿的胰岛素产生/分泌这些具体目标旨在 确定胰腺内分泌发育和生长的关键期 确定宫内发育迟缓对绵羊模型胰岛功能的影响 环境因素(由中度高热引起)胎盘功能不全 (PI)。将确定胎儿低血糖和低氨基酸血症的发病情况 并检查胰腺发育和功能。新陈代谢研究将 妊娠期PI-IUGR胎儿的体内和体外研究 评估β细胞功能的生理学技术。此外，形态 将对发育中的胰腺(胰岛)进行检查，以确定发生的变化 细胞组成，并确定特定的发育机制 参与胰岛素的分泌。这些研究对于确定如何 IUGR导致胰腺发育异常和胰岛素分泌减少 在以后的生活中可能会导致病理改变的能力。

DESCRIPTION (provided by applicant): Intrauterine growth restriction (IUGR) increases the relative risk for perinatal morbidity and mortality, and epidemiological evidence suggests a predisposition for adult onset diseases related to fetal metabolic abnormalities. Perturbations in pancreatic development due to IUGR may lead to an inappropriate beta cell ontogeny resulting in a population of beta cells that are unable to cope with metabolic stress. The long-term goal of this project is to understand mechanisms underlying abnormal pancreatic development and/or function leading to reduced insulin production/secretion in IUGR infants. The specific aims are designed to define critical periods of pancreatic endocrine development and growth and determine the effects on islet function in a sheep model of IUGR resulting from environmentally induced (by moderate hyperthermia) placental insufficiency (PI). The onset of fetal hypoglycemia and hypoaminoacidemia will be determined and pancreatic development and function examined. Metabolic studies will be conducted during gestation in the PI-IUGR fetus using in vivo and in vitro physiological techniques to assess beta cell function. Additionally, morphology of developing pancreas (islets) will be examined to identify changes occurring in cellular composition and to identify specific developmental mechanisms involved in insulin secretion. These studies are crucial for determining how IUGR leads to abnormal pancreatic development and decreased insulin secretion capacity that may potentially contribute to pathology in later life.