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Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS

Thyroid hormones are normally involved in glycaemic control, but their excess can lead to altered glucose metabolism and insulin resistance (IR). Since hyperthyroidism-linked increase in ROS results in tissue oxidative stress that is considered a hallmark of conditions leading to IR, it is conceivab...

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Autores principales: Fasciolo, Gianluca, Napolitano, Gaetana, Aprile, Marianna, Cataldi, Simona, Costa, Valerio, Ciccodicola, Alfredo, Di Meo, Sergio, Venditti, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311543/
https://www.ncbi.nlm.nih.gov/pubmed/35883786
http://dx.doi.org/10.3390/antiox11071295
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author Fasciolo, Gianluca
Napolitano, Gaetana
Aprile, Marianna
Cataldi, Simona
Costa, Valerio
Ciccodicola, Alfredo
Di Meo, Sergio
Venditti, Paola
author_facet Fasciolo, Gianluca
Napolitano, Gaetana
Aprile, Marianna
Cataldi, Simona
Costa, Valerio
Ciccodicola, Alfredo
Di Meo, Sergio
Venditti, Paola
author_sort Fasciolo, Gianluca
collection PubMed
description Thyroid hormones are normally involved in glycaemic control, but their excess can lead to altered glucose metabolism and insulin resistance (IR). Since hyperthyroidism-linked increase in ROS results in tissue oxidative stress that is considered a hallmark of conditions leading to IR, it is conceivable a role of ROS in the onset of IR in hyperthyroidism. To verify this hypothesis, we evaluated the effects of vitamin E on thyroid hormone-induced oxidative damage, insulin resistance, and on gene expression of key molecules involved in IR in the rat liver. The factors involved in oxidative damage, namely the total content of ROS, the mitochondrial production of ROS, the activity of antioxidant enzymes, the in vitro susceptibility to oxidative stress, have been correlated to insulin resistance indices, such as insulin activation of hepatic Akt and plasma level of glucose, insulin and HOMA index. Our results indicate that increased levels of oxidative damage ROS content and production and susceptibility to oxidative damage, parallel increased fasting plasma level of glucose and insulin, reduced activation of Akt and increased activation of JNK. This last result suggests a role for JNK in the insulin resistance induced by hyperthyroidism. Furthermore, the variation of the genes Pparg, Ppara, Cd36 and Slc2a2 could explain, at least in part, the observed metabolic phenotypes.
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spelling pubmed-93115432022-07-26 Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS Fasciolo, Gianluca Napolitano, Gaetana Aprile, Marianna Cataldi, Simona Costa, Valerio Ciccodicola, Alfredo Di Meo, Sergio Venditti, Paola Antioxidants (Basel) Article Thyroid hormones are normally involved in glycaemic control, but their excess can lead to altered glucose metabolism and insulin resistance (IR). Since hyperthyroidism-linked increase in ROS results in tissue oxidative stress that is considered a hallmark of conditions leading to IR, it is conceivable a role of ROS in the onset of IR in hyperthyroidism. To verify this hypothesis, we evaluated the effects of vitamin E on thyroid hormone-induced oxidative damage, insulin resistance, and on gene expression of key molecules involved in IR in the rat liver. The factors involved in oxidative damage, namely the total content of ROS, the mitochondrial production of ROS, the activity of antioxidant enzymes, the in vitro susceptibility to oxidative stress, have been correlated to insulin resistance indices, such as insulin activation of hepatic Akt and plasma level of glucose, insulin and HOMA index. Our results indicate that increased levels of oxidative damage ROS content and production and susceptibility to oxidative damage, parallel increased fasting plasma level of glucose and insulin, reduced activation of Akt and increased activation of JNK. This last result suggests a role for JNK in the insulin resistance induced by hyperthyroidism. Furthermore, the variation of the genes Pparg, Ppara, Cd36 and Slc2a2 could explain, at least in part, the observed metabolic phenotypes. MDPI 2022-06-29 /pmc/articles/PMC9311543/ /pubmed/35883786 http://dx.doi.org/10.3390/antiox11071295 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fasciolo, Gianluca
Napolitano, Gaetana
Aprile, Marianna
Cataldi, Simona
Costa, Valerio
Ciccodicola, Alfredo
Di Meo, Sergio
Venditti, Paola
Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS
title Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS
title_full Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS
title_fullStr Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS
title_full_unstemmed Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS
title_short Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS
title_sort hepatic insulin resistance in hyperthyroid rat liver: vitamin e supplementation highlights a possible role of ros
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311543/
https://www.ncbi.nlm.nih.gov/pubmed/35883786
http://dx.doi.org/10.3390/antiox11071295
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