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High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo

Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA) affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to b...

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Autores principales: Zhi, Li, Yuzhang, Zhu, Tianliang, Huang, Hisatome, Ichiro, Yamamoto, Tetsuya, Jidong, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737875/
https://www.ncbi.nlm.nih.gov/pubmed/26836389
http://dx.doi.org/10.1371/journal.pone.0147737
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author Zhi, Li
Yuzhang, Zhu
Tianliang, Huang
Hisatome, Ichiro
Yamamoto, Tetsuya
Jidong, Cheng
author_facet Zhi, Li
Yuzhang, Zhu
Tianliang, Huang
Hisatome, Ichiro
Yamamoto, Tetsuya
Jidong, Cheng
author_sort Zhi, Li
collection PubMed
description Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA) affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS) production. Western blot analysis was used to examine the levels of insulin receptor (IR), phosphorylated insulin receptor substrate 1 (IRS1, Ser307) and phospho-Akt (Ser473). We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307) and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307) response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307) and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.
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spelling pubmed-47378752016-02-04 High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo Zhi, Li Yuzhang, Zhu Tianliang, Huang Hisatome, Ichiro Yamamoto, Tetsuya Jidong, Cheng PLoS One Research Article Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA) affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS) production. Western blot analysis was used to examine the levels of insulin receptor (IR), phosphorylated insulin receptor substrate 1 (IRS1, Ser307) and phospho-Akt (Ser473). We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307) and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307) response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307) and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease. Public Library of Science 2016-02-02 /pmc/articles/PMC4737875/ /pubmed/26836389 http://dx.doi.org/10.1371/journal.pone.0147737 Text en © 2016 Zhi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhi, Li
Yuzhang, Zhu
Tianliang, Huang
Hisatome, Ichiro
Yamamoto, Tetsuya
Jidong, Cheng
High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo
title High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo
title_full High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo
title_fullStr High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo
title_full_unstemmed High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo
title_short High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo
title_sort high uric acid induces insulin resistance in cardiomyocytes in vitro and in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737875/
https://www.ncbi.nlm.nih.gov/pubmed/26836389
http://dx.doi.org/10.1371/journal.pone.0147737
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