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的重要组成部分。果糖被一种叫做GLUT5的肠道蛋白质吸收，这种蛋白质在新生哺乳动物中是没有的。断奶时，哺乳动物的饮食由牛奶转变为固体食物，肠道内灌注果糖刺激肠细胞中GLUT5 mRNA和蛋白的制造，使果糖的吸收率增加。在这个阶段，仅果糖就足以刺激GLUT5的出现，而激素似乎并不参与其中。在哺乳期，哺乳动物的饮食完全由母亲的乳汁组成，肠道灌注果糖不能刺激GLUT5，必须在果糖刺激GLUT5合成之前给药糖皮质激素家族。因此，糖皮质激素就像“年龄”一样，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”是否各自刺激了与果糖诱导GLUT5表达相同的机制。该项目将收集与适应机制相关的信息，这些机制允许肠道在发育过程中快速改变功能，从而使其能够快速响应环境信号。在突然将水果引入饮食后，肠道的快速适应使其能够吸收果糖。美国人每日能量摄入的10%以上来自果糖，而最近果糖摄入量的增加与肥胖和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肥胖流行的营养素代谢的理解，以及哺乳动物肠道利用的机制来适应出生时发生的营养转变。在这项研究的过程中，将为高中生、本科生和研究生提供培训机会，其中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.