title: Dysregulated hepatic expression of glucose transporters in chronic disease: contribution of semicarbazide-sensitive amine oxidase to hepatic glucose uptake.
abstract: Insulin resistance is common in patients with chronic liver disease (CLD). Serum levels of soluble vascular adhesion protein-1 (VAP-1) are also increased in these patients. The amine oxidase activity of VAP-1 stimulates glucose uptake via translocation of transporters to the cell membrane in adipocytes and smooth muscle cells. We aimed to document human hepatocellular expression of glucose transporters (GLUTs) and to determine if VAP-1 activity influences receptor expression and hepatic glucose uptake. Quantitative PCR and immunocytochemistry were used to study human liver tissue and cultured cells. We also used tissue slices from humans and VAP-1-deficient mice to assay glucose uptake and measure hepatocellular responses to stimulation. We report upregulation of GLUT1, -3, -5, -6, -7, -8, -9, -10, -11, -12, and -13 in CLD. VAP-1 expression and enzyme activity increased in disease, and provision of substrate to hepatic VAP-1 drives hepatic glucose uptake. This effect was sensitive to inhibition of VAP-1 and could be recapitulated by H2O2. VAP-1 activity also altered expression and subcellular localization of GLUT2, -4, -9, -10, and -13. Therefore, we show, for the first time, alterations in hepatocellular expression of glucose and fructose transporters in CLD and provide evidence that the semicarbazide-sensitive amine oxidase activity of VAP-1 modifies hepatic glucose homeostasis and may contribute to patterns of GLUT expression in chronic disease.
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Sumera
authors.initials: S
authors.lastname: Karim
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Liaskou
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Janine
authors.initials: J
authors.lastname: Fear
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Abhilok
authors.initials: A
authors.lastname: Garg
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Gary
authors.initials: G
authors.lastname: Reynolds
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Lee
authors.initials: L
authors.lastname: Claridge
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham, United Kingdom.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Newsome
authors.affiliation: Centre for Liver Research and National Institute for Health Research Biomedical Research Unit, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; and p.f.lalor@bham.ac.uk.
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Lalor
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout
chemical_list: D015815:Cell Adhesion Molecules; D051246:Glucose Transport Proteins, Facilitative; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D005947:Glucose
keywords: chronic disease; glucose transporter; human; liver; vascular adhesion protein-1