Date of Award

Fall 2007

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering - (M.S.)

Department

Biomedical Engineering

First Advisor

Ronaldo P. Ferraris

Second Advisor

William Corson Hunter

Third Advisor

Treena Livingston Arinzeh

Abstract

Regulation of GLUT5 is dependent on the presence of its substrate, fructose, but it is also correlated with the developmental (aging) process of the intestine. To identify fructose-responsive genes whose expression also changes with age, intestines of 10 and 20 d old pups were perfused, by Ferraris et al., with fructose and then compared by microarray analysis. From this, a gene clustering analysis revealed that some age- and fructose-specific genes are regulated by corticosterones, which normally increase in pups ≥ 14 d old. Subsequent work indicated that priming the gut with Dexamethasone (Dex, a glucocorticoid analog) allowed fructose to precociously stimulate GLUT5 even in suckling pups < 14 d old.

This suggests that the effect of Dex on GLUT5 is similar to the effect of age; both allow fructose to stimulate GLUT5. It is not known: (1) if this similar effect of Dex and age is specific to GLUT5 or if it could be extended to a larger family of genes, and (2) is Dex and age are acting through the same or different signaling mechanisms. In this study I tested the hypothesis that Dex allows fructose to stimulate GLUT5 by inducing the same genes as those induced by age. I therefore, determined by microarray analysis in 10 old suckling pups, the identity of genes that are regulated solely by fructose, solely by Dex and by Dex under fructose conditions. Genes regulated by Dex under fructose conditions were compared to genes regulated by age in the presence of fructose, which were identified in a previous microarray experiment by Douard et al.

Microarray results revealed 29 genes up-regulated by Dex, 14 by fructose, and 10 by Dex under fructose conditions. There were 64 genes down-regulated by fructose, 18 by Dex and 2 by Dex under Fructose conditions. Of these 12 Dex- under fructose conditions- sensitive genes there were no genes that were also age and fructose sensitive. There were however, four genes that were regulated by both age and Dex, independently of fructose. Hence, while there are common regulatory factors between age and Dex, the different populations of Dex- and age- sensitive intermediates, under fructose influence, suggest that there are alternative signaling pathways leading to the same outcome: an earlier onset of GLUT5 in the brushborder membrane of the small intestine.

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