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Role of metabolism and intracellular trafficking in fructose‐induced GLUT5 regulation (822.4)
Author(s) -
Patel Chirag,
Douard Veronique,
Tharabenjasin P,
Topaktas E,
Ferraris Ronaldo
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.822.4
Subject(s) - intracellular , fructose , downregulation and upregulation , metabolism , glucose transporter , chemistry , carbohydrate metabolism , small intestine , biochemistry , microbiology and biotechnology , biology , endocrinology , insulin , gene
Marked increases in fructose consumption have been linked to various diseases. Fructose (F) upregulates its own absorption by increasing the expression & activity of the intestinal F transporter GLUT5, but the underlying mechanism is not well understood. Defects or limits in regulation can lead to adult‐onset F intolerance or to F malabsorption in infants. I tested the hypothesis that F transport via GLUT5, metabolism via ketohexokinase (KHK), and GLUT5 intracellular trafficking to the apical membrane via the GTPase Rab11a are required for GLUT5 upregulation. WAdult wildtype (wt), GLUT5‐/‐, and KHK‐/‐, and Rab11a‐/‐ mice were receivedreceiving 30% glucose (G), fructose (F) or lysine (L) by gavage twice a d for 3 d at X.X ml/kgays. 17 d old wt and Rab11a‐/‐ mice were gavaged with either 30% G or F. Afterwards, GLUT5 activity as well as mRNA and protein expression determined in the small intestine. Activity and expression of GLUT5 and of other enzymes involved in F metabolism increased in F‐gavaged mice compared to those gavaged with G or L. This effect was specific because expression of unrelated transporters like SGLT1 did not change. Strikingly, F failed to induce the expression & activity of GLUT5 and of other enzymes involved in F metabolism, in KHK‐/‐, GLUT5‐/‐ and Rab11a‐/‐ mice. Thus, I have demonstrated for the first time the essential roles of membrane transport, metabolism, and Rab11a‐mediated trafficking in F‐ induced GLUT5 upregulation. Grant Funding Source : NSF IOS‐1121049.