Developmental Regulation of Intestinal Sugar Transport

水果中的糖被称为果糖，它是人类和其他哺乳动物饮食中的重要组成部分。果糖被一种名为GLUT5的肠道蛋白质吸收，这种蛋白质在新生哺乳动物中没有发现。在断奶期间，当哺乳动物的饮食从牛奶转变为固体食物时，肠道中果糖的灌流刺激了肠道细胞中GLUT5基因和蛋白质的产生，从而增加了果糖的吸收速度。在这个阶段，仅果糖就足以刺激GLUT5的出现，激素似乎不参与其中。在哺乳期，当哺乳动物的饮食完全由母亲的牛奶组成时，用果糖进行肠道灌流不能刺激GLUT5，必须在果糖刺激GLUT5合成之前给予糖皮质激素家族。因此，糖皮质激素，如“年龄”，允许果糖调节GLUT5。这项工作的总体目标是确定糖皮质激素和“年龄”是否各自刺激(S)允许果糖(S)诱导GLUT5表达的相同机制。该项目将收集与适应机制有关的信息，使肠道在发育过程中迅速改变功能，从而使其能够对环境信号做出快速反应。在饮食中突然引入水果后，快速适应使肠道能够吸收果糖。美国人每天摄入的能量中有10%以上来自果糖，最近果糖消费量的增加与肥胖症和II型糖尿病发病率的显著增加密切相关。因此，这个项目增加了我们对导致美国人肥胖流行的一种营养物质的新陈代谢，以及哺乳动物肠道用来适应出生期间发生的营养转变的机制的了解。在这项研究的过程中，培训机会将提供给高中生、本科生和研究生，他们中的许多人来自科学界代表性不足的群体。

The sugar in fruits is called fructose and it is an important constituent of the diet of humans and other mammals. Fructose is absorbed by an intestinal protein called GLUT5 that is not found in newborn mammals. During weaning when the mammalian diet changes from milk to solid food, intestinal perfusion of fructose stimulates the manufacture of GLUT5 mRNA and protein in intestinal cells, so that the rate of fructose absorption increases. At this stage, fructose alone is sufficient to stimulate the appearance of GLUT5, and hormones do not seem to be involved. During the suckling stage when the mammalian diet consists entirely of milk from the mother, intestinal perfusion with fructose cannot stimulate GLUT5, and the hormone family of glucocorticoids must be administered before fructose can stimulate GLUT5 synthesis. Hence, glucocorticoids, like "age", allow fructose to regulate GLUT5. The general objective of this work is to determine whether glucocorticoids and "age" each stimulate the same mechanism(s) that allow(s) fructose to induce GLUT5 expression. This project will gather information related to mechanisms of adaptation that allow the gut to rapidly change function during development, thereby enabling it to respond rapidly to environmental signals. A rapid adaptation enables the intestine to absorb fructose after a sudden introduction of fruits to the diet. More than 10% of the daily energy intake by Americans is derived from fructose, and recent increases in fructose consumption are tightly linked to marked increases in incidence of obesity and type II diabetes. Hence, this project increases our understanding of the metabolism of a nutrient that contributes to the obesity epidemic in Americans, and of the mechanisms the mammalian intestine utilizes to adapt to nutritional transitions occurring during birth. During the course of this research training opportunities will be made available to high school, undergraduate, and graduate students, many of whom are from groups underrepresented in science.