Cargando…
Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance
SIRT1 is a NAD(+)-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influen...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370576/ https://www.ncbi.nlm.nih.gov/pubmed/25798922 http://dx.doi.org/10.1371/journal.pone.0121959 |
_version_ | 1782362893076922368 |
---|---|
author | Brandon, Amanda E. Tid-Ang, Jennifer Wright, Lauren E. Stuart, Ella Suryana, Eurwin Bentley, Nicholas Turner, Nigel Cooney, Gregory J. Ruderman, Neil B. Kraegen, Edward W. |
author_facet | Brandon, Amanda E. Tid-Ang, Jennifer Wright, Lauren E. Stuart, Ella Suryana, Eurwin Bentley, Nicholas Turner, Nigel Cooney, Gregory J. Ruderman, Neil B. Kraegen, Edward W. |
author_sort | Brandon, Amanda E. |
collection | PubMed |
description | SIRT1 is a NAD(+)-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia. |
format | Online Article Text |
id | pubmed-4370576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43705762015-04-04 Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance Brandon, Amanda E. Tid-Ang, Jennifer Wright, Lauren E. Stuart, Ella Suryana, Eurwin Bentley, Nicholas Turner, Nigel Cooney, Gregory J. Ruderman, Neil B. Kraegen, Edward W. PLoS One Research Article SIRT1 is a NAD(+)-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia. Public Library of Science 2015-03-23 /pmc/articles/PMC4370576/ /pubmed/25798922 http://dx.doi.org/10.1371/journal.pone.0121959 Text en © 2015 Brandon 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Brandon, Amanda E. Tid-Ang, Jennifer Wright, Lauren E. Stuart, Ella Suryana, Eurwin Bentley, Nicholas Turner, Nigel Cooney, Gregory J. Ruderman, Neil B. Kraegen, Edward W. Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance |
title | Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance |
title_full | Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance |
title_fullStr | Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance |
title_full_unstemmed | Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance |
title_short | Overexpression of SIRT1 in Rat Skeletal Muscle Does Not Alter Glucose Induced Insulin Resistance |
title_sort | overexpression of sirt1 in rat skeletal muscle does not alter glucose induced insulin resistance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370576/ https://www.ncbi.nlm.nih.gov/pubmed/25798922 http://dx.doi.org/10.1371/journal.pone.0121959 |
work_keys_str_mv | AT brandonamandae overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT tidangjennifer overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT wrightlaurene overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT stuartella overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT suryanaeurwin overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT bentleynicholas overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT turnernigel overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT cooneygregoryj overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT rudermanneilb overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance AT kraegenedwardw overexpressionofsirt1inratskeletalmuscledoesnotalterglucoseinducedinsulinresistance |