Developmental Regulation of Intestinal Sugar Transport

点击翻译按钮获取中文摘要

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.