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Regulation of the Primary Intestinal Fructose Transporter GLUT5 is Dependent on Metabolism by FK and on Trafficking by Rab11a‐dependent Endosomes
Author(s) -
Patel C,
Douard V.,
Gao N.,
Yu S.,
Ferraris R.
Publication year - 2015
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.29.1_supplement.848.4
Subject(s) - glucose transporter , downregulation and upregulation , endosome , fructose , biochemistry , chemistry , carbohydrate metabolism , glycolysis , metabolism , biology , microbiology and biotechnology , endocrinology , insulin , cell , gene
Identifying the mechanisms underlying the regulation by dietary fructose (F) of the F transporter GLUT5 ( Slc2a5 ) and of F metabolizing enzymes (FMEs) is essential in understanding the metabolic diseases ascribed to excessive F intake. We tested the hypotheses that F transport via GLUT5, F metabolism via fructokinase (FK) and GLUT5 trafficking to the apical membrane via GTPase Rab11a‐dependent endosomes are required for fructose‐induced upregulation of GLUT5 and FMEs. To induce GLUT5, 30% F and control solutions @ 0.2 ml/mouse were gavage‐fed 2X/d for 2.5 d to mice with ad libitum access to food. In wildtype mice, F but not lysine or glucose dramatically increased the hnRNA, mRNA, and protein expression as well as activity of GLUT5, gluconeogenic and FMEs but not those of nonFMEs and of putative F transporters GLUTs 7, 8 and 12 whose expression was ~100‐fold less than that of GLUT5. Thus, luminal F specifically activated the transcription of Slc2a5 . Deletion of GLUT5 abolished F transport and prevented the upregulation of FMEs. Preventing F metabolism by deletion of FK stopped F from upregulating GLUT5, gluconeogenic and FMEs but had no effect on nonFMEs. The downstream F metabolite, glyceraldehyde, was not the regulatory signal as it increased GLUT5 activity but not expression. Impeding GLUT5 trafficking to the apical membrane using Rab11aΔIEC mice that had no Rab11a in enterocytes, not only prevented the F‐induced upregulation of GLUT5 but also reduced its baseline transport activity. Dietary regulation of GLUT5 and of gluconeogenic and FMEs requires F transport, F metabolism, and Rab11a‐mediated GLUT5 trafficking to the apical membrane (NSF‐IOS1121049, NIH‐DK102934)