Regulation of intestinal fructose transport in neonatal rats

本研究将研究肠道营养转运系统如何适应出生和断奶时营养类型和浓度的显著变化。出生时，小肠突然获得了一项新功能：从牛奶中吸收营养。在断奶期间，肠道必须制造不同类型或不同数量的转运蛋白。肠细胞是如何制造和“知道”何时制造这些转运蛋白的？该项目的长期目标是确定发育过程中肠道营养物质运输的调节机制。肠道果糖转运体GLUT5通常在断奶后才产生。然而，过早地引入其底物，膳食果糖，显著地诱导了这种转运体的早期出现。该项目将确定在断奶期间果糖刺激GLUT5时改变其表达的基因。然后，它将通过使用细胞渗透性、刺激或抑制其作用的药理学制剂，确定哪些因素介导了膳食果糖的作用。如果这些药物改变了果糖对GLUT5的影响，那么它们的靶蛋白可能在将饮食信号转导到GLUT5基因中发挥重要作用。这些因子在肠道中的位置将通过含有染料的探针来确定，这些探针可以特异性地识别它们。因此，本研究结果将为了解发育过程中营养转运体的调控提供重要的新信息。此外，通过研究控制肠道发育的营养反应性调节机制，该项目可以确定重新编程正常吸收发育模式的潜力，从而使肠道在发育的早期阶段处理营养物质。这一知识将增加我们对控制早产儿肠道生长和成熟机制的理解。果糖是美国人饮食中非常常见的成分，这些研究具有重要的营养意义。此外，该项目还将支持博士后和学生的培训和教育。

This study will examine how intestinal nutrient transport systems adapt to marked changes in nutrient types and concentrations occurring at birth and at weaning. At birth, the small intestine abruptly acquires a new function: to absorb nutrients from milk. During weaning, the intestine has to manufacture different types or different numbers of transporters. How do intestinal cells make, and 'know' when to make, these transporters? The long-term objective of this project is to determine the mechanisms regulating intestinal nutrient transport during development. The intestinal fructose transporter GLUT5 is normally not made until after completion of weaning. However, precocious introduction of its substrate, dietary fructose, dramatically induces the early appearance of this transporter. This project will determine the genes that change their expression when fructose stimulates GLUT5 during weaning. It will then identify which of these factors mediate the effect of dietary fructose by using cell-permeable, pharmacological agents that stimulate or inhibit their action. If these agents alter the effect of fructose on GLUT5, then their target proteins likely play important roles in transducing the dietary signal to the GLUT5 gene. The location of these factors in the intestine will be determined by dye-containing probes that specifically recognize them. Thus, the results of this study will provide important new information to understand the regulation of nutrient transporters during development. In addition, by examining nutrient-responsive regulatory mechanisms controlling gut development, this project can determine the potential of reprogramming normal developmental patterns of absorption in order to allow the intestine to process nutrients at an earlier stage of development. This knowledge would increase our understanding of mechanisms that control intestinal growth and maturation in premature infants. Fructose is a very common ingredient in American diets, and these studies have major nutritional significance. Further, this project will also support the training and education of postdoctoral fellows and students.