Fetal pancreatic development & insulin secretion

胎儿胰腺发育

• 批准号: 6882715
• 负责人: William W Hay
• 金额: $ 51.93万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6882715
• 关键词: SCID mouse; aminoacid; cell transplantation; diet therapy; embryo /fetus; embryogenesis; gene expression; glucose; histogenesis; hormone regulation /control mechanism; hormone therapy; immunocytochemistry; insulin; insulinlike growth factor; mammalian embryology; metabolism; mother /embryo /fetus nutrition; nonhuman therapy evaluation; northern blottings; nutrient interaction; nutrition related tag; pancreas; pancreatic islet function; prenatal growth disorder; sheep; western blottings

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.

描述：（由申请人提供）本研究项目的目标是