Effects of diet on metabolic programming of glucose homeostasis

我的NSERC资助的研究项目致力于了解生长和发育的不同关键时期在多大程度上容易因不适当的营养摄入而受到不利代谢编程的影响。 在这种情况下，编程被定义为功能的永久性变化，发生在发育过程中的营养摄入量的变化。 我的研究探讨了过度或不适当的营养供应在敏感时期的发展，这是在当代加拿大社会高度相关的影响。在这个赠款周期解决的具体目标是：1）确定母亲摄入简单碳水化合物的程度（特别是果糖（FR）或葡萄糖（GLU））导致胎儿发育期间营养物质可用性的改变，和2）表征后代胰腺和骨骼肌的代谢程序。 我将使用给予10%FR或GLU溶液代替饮用水的雌性大鼠作为实验模型。 初步数据表明，给予FR溶液的大鼠母鼠在妊娠期间血糖和胰岛素浓度出现轻度至中度升高，证实发育中胎儿的营养可用性发生了改变。 孕妇和胎儿的血液，沿着羊水将被采样，以检查怀孕期间的营养供应。胎盘中营养转运蛋白的表达将补充这一评估。 在后代中，体内和体外技术的组合将被用来确定对胰腺结构和功能的影响沿着骨骼肌的变化，骨骼肌是全身葡萄糖代谢的主要贡献者。这些研究将是第一批研究增加简单碳水化合物摄入对影响胎儿发育机制的影响以及对后代葡萄糖稳态的长期影响的研究。 研究结果对于理解基本的人类生物学意义重大，并可应用于临床营养沿着更广泛的公共卫生政策。

My NSERC-funded research program is dedicated to understanding the extent to which different critical periods of growth and development are susceptible to adverse metabolic programming through inappropriate nutritional intake.  In this context, programming is defined as the permanent changes in function that occur as the result of modified nutritional intake during development.  My research examines the effects of excessive or inappropriate nutrient availability during sensitive periods of development, which is highly relevant in contemporary Canadian society.Specific objectives addressed in this grant cycle are to: 1) determine the extent to which maternal intake of simple carbohydrates (specifically fructose (FR) or glucose (GLU)) leads to alterations in nutrient availability during fetal development, and 2) characterize metabolic programming of the pancreas and skeletal muscle in offspring.  I will use female rats given a 10% FR or GLU solution in place of drinking water as the experimental model.  Pilot data indicates that rat dams give a FR solution experience mild-moderate elevations in their blood glucose and insulin concentrations during pregnancy, confirming that nutrient availability to the developing fetus is altered.  Maternal and fetal blood, along with amniotic fluid will be sampled to examine nutrient availability during pregnancy. Nutrient transport protein expression in placenta will complement this assessment.  In offspring, a combination of in vivo and in vitro techniques will be used to determine effects on pancreatic structure and function along with changes incurred in skeletal muscle, a primary contributor to whole-body glucose metabolism.These studies will be among the first to examine effects enhanced simple carbohydrate intake on mechanisms affecting fetal development in combination with the long-term impact on glucose homeostasis in offspring.  Results are significant for understanding basic human biology and have application to clinical nutrition along with broader public health policies.