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Fructose-induced stress signaling in the liver involves methylglyoxal

BACKGROUND: Fructose produces hepatic insulin resistance in humans and animals. We have proposed that the selective metabolism of fructose by the liver can, under conditions of elevated fructose delivery, inflict a metabolic insult that is localized to the hepatocyte. The present study was designed...

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Autores principales: Wei, Yuren, Wang, Dong, Moran, Gretchen, Estrada, Andrea, Pagliassotti, Michael J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635994/
https://www.ncbi.nlm.nih.gov/pubmed/23566306
http://dx.doi.org/10.1186/1743-7075-10-32
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author Wei, Yuren
Wang, Dong
Moran, Gretchen
Estrada, Andrea
Pagliassotti, Michael J
author_facet Wei, Yuren
Wang, Dong
Moran, Gretchen
Estrada, Andrea
Pagliassotti, Michael J
author_sort Wei, Yuren
collection PubMed
description BACKGROUND: Fructose produces hepatic insulin resistance in humans and animals. We have proposed that the selective metabolism of fructose by the liver can, under conditions of elevated fructose delivery, inflict a metabolic insult that is localized to the hepatocyte. The present study was designed to identify potential cellular effectors of this insult. METHODS: Primary hepatocytes were incubated with 8 mM glucose and 0.12% inulin (G, n = 6) or 8 mM glucose, 0.12% inulin and 28 mU of inulinase (GF, n = 6) in the presence or absence of insulin for 0, 2, or 4 h. RESULTS: GF produced fructose concentrations of ~0.7 mM over the 4 h experiment. GF induced phosphorylation of MKK7 and JNK, phosphorylation of serine307 on IRS-1, and reduced tyrosine phosphorylation of IRS-1 and -2. GF increased ceramide levels and reactive oxygen species (ROS); however inhibitors of ceramide synthesis or ROS accumulation did not prevent GF-mediated changes in MKK7, JNK or IRS proteins. GF increased cellular methylglyoxal concentrations and a selective increase in methylglyoxal recapitulated the GF-induced changes in MKK7, JNK and IRS proteins. CONCLUSIONS: We hypothesize that GF-mediated changes in stress signaling involve methylglyoxal in primary hepatocytes.
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spelling pubmed-36359942013-04-26 Fructose-induced stress signaling in the liver involves methylglyoxal Wei, Yuren Wang, Dong Moran, Gretchen Estrada, Andrea Pagliassotti, Michael J Nutr Metab (Lond) Research BACKGROUND: Fructose produces hepatic insulin resistance in humans and animals. We have proposed that the selective metabolism of fructose by the liver can, under conditions of elevated fructose delivery, inflict a metabolic insult that is localized to the hepatocyte. The present study was designed to identify potential cellular effectors of this insult. METHODS: Primary hepatocytes were incubated with 8 mM glucose and 0.12% inulin (G, n = 6) or 8 mM glucose, 0.12% inulin and 28 mU of inulinase (GF, n = 6) in the presence or absence of insulin for 0, 2, or 4 h. RESULTS: GF produced fructose concentrations of ~0.7 mM over the 4 h experiment. GF induced phosphorylation of MKK7 and JNK, phosphorylation of serine307 on IRS-1, and reduced tyrosine phosphorylation of IRS-1 and -2. GF increased ceramide levels and reactive oxygen species (ROS); however inhibitors of ceramide synthesis or ROS accumulation did not prevent GF-mediated changes in MKK7, JNK or IRS proteins. GF increased cellular methylglyoxal concentrations and a selective increase in methylglyoxal recapitulated the GF-induced changes in MKK7, JNK and IRS proteins. CONCLUSIONS: We hypothesize that GF-mediated changes in stress signaling involve methylglyoxal in primary hepatocytes. BioMed Central 2013-04-08 /pmc/articles/PMC3635994/ /pubmed/23566306 http://dx.doi.org/10.1186/1743-7075-10-32 Text en Copyright © 2013 Wei et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Wei, Yuren
Wang, Dong
Moran, Gretchen
Estrada, Andrea
Pagliassotti, Michael J
Fructose-induced stress signaling in the liver involves methylglyoxal
title Fructose-induced stress signaling in the liver involves methylglyoxal
title_full Fructose-induced stress signaling in the liver involves methylglyoxal
title_fullStr Fructose-induced stress signaling in the liver involves methylglyoxal
title_full_unstemmed Fructose-induced stress signaling in the liver involves methylglyoxal
title_short Fructose-induced stress signaling in the liver involves methylglyoxal
title_sort fructose-induced stress signaling in the liver involves methylglyoxal
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635994/
https://www.ncbi.nlm.nih.gov/pubmed/23566306
http://dx.doi.org/10.1186/1743-7075-10-32
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