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Dysregulated hepatic expression of glucose transporters in chronic disease:
contribution of semicarbazide-sensitive amine oxidase to hepatic glucose uptake
#MMPMID25342050
Karim S
; Liaskou E
; Fear J
; Garg A
; Reynolds G
; Claridge L
; Adams DH
; Newsome PN
; Lalor PF
Am J Physiol Gastrointest Liver Physiol
2014[Dec]; 307
(12
): G1180-90
PMID25342050
show ga
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.
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