Fetal pancreatic development & insulin secretion

说明：（申请人提供）本研究项目的目标是 了解调节胰腺发育和功能的机制， 受营养素和次级内分泌因素的影响， 营养素的影响，并特别关注有限的胰腺生长 和功能在胎儿宫内生长受限（IUGR）。我们将 验证胎盘功能不全导致胎儿营养减少的假设 将导致主要营养素（葡萄糖）和次要激素（胰岛素， 胰岛素样生长因子（IGFs）缺乏导致胰腺内分泌发育异常， 有三个具体目标。 1.分析胰腺发育和功能，以确定关键发育 时期，并确定适应所施加的养分供应减少 在IUGR胎儿中。 2.确定营养和激素缺乏对胰岛素的影响 在IUGR胎儿胰腺内分泌细胞中的产生和分泌。 3.通过以下方式测试恢复正常胰腺发育和功能的能力： 关键时期的体内营养和激素补充 IUGR胎儿的发育。 拟议的研究将在我们的IUGR绵羊模型中进行， 母亲在怀孕期间暴露于中度高温环境。 这些胎儿会发生低血糖和低氨基酸血症， 在妊娠的后三分之一胰岛素和GF浓度的不足。 体内和体外研究将表征胰腺发育， 功能和确定机制负责胰腺异常， 是胎儿营养缺乏的直接后果这些研究还将 深入了解临床干预的要求，以改善 IUGR胎儿和新生儿的胰腺功能不全， 胎儿和新生儿的发病率和死亡率，并有可能减少 与低出生率有关的成人发病率 重量.

DESCRIPTION: (Provided By Applicant)The goal of this research project is to understand mechanisms regulating pancreatic development and function that are influenced by nutrients and secondary endocrine factors that augment the effects of nutrients and to focus specifically on the limited pancreatic growth and function in fetuses with intrauterine growth restriction (IUGR). We will test the hypothesis that reduced fetal nutrition from placental insufficiency will result in primary nutrient (glucose) and secondary hormonal (insulin, IGFs) deficiencies that lead to abnormal pancreatic endocrine development and function with 3 specific aims. 1. Analyze pancreatic development and function to define critical developmental periods and identify the adaptations imposed by decreased nutrient availability in the IUGR fetus. 2. Determine the effects of nutrient and hormonal deficiencies on insulin production and secretion in pancreatic endocrine cells in the IUGR fetus. 3. Test the ability to restore normal pancreatic development and function by in vivo nutrient and hormonal supplementation during critical periods of development in the IUGR fetus. The proposed studies will be conducted in our ovine model of IUGR produced by maternal exposure to a moderately hyperthermic environment during gestation. These fetuses develop hypoglycemia and hypoaminoacidemia and secondary deficiencies in insulin and GF concentrations in the latter third of gestation. in vivo and in vitro studies will characterize pancreatic development and function and determine mechanisms responsible for pancreatic abnormalities that are direct consequences of fetal nutrient deprivation. The studies also will provide insight into requirements for clinical interventions to ameliorate pancreatic insufficiency in IUGR fetuses and neonates, hopefully to reduce fetal and neonatal morbidity and mortality, and potentially to reduce the incidence of adult onset diseases that have been associated with low birth weight.