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 influence...
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Public Library of Science (PLoS)
2015-01-01
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Online Access: | http://europepmc.org/articles/PMC4370576?pdf=render |
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author | Amanda E Brandon Jennifer Tid-Ang Lauren E Wright Ella Stuart Eurwin Suryana Nicholas Bentley Nigel Turner Gregory J Cooney Neil B Ruderman Edward W Kraegen |
author_facet | Amanda E Brandon Jennifer Tid-Ang Lauren E Wright Ella Stuart Eurwin Suryana Nicholas Bentley Nigel Turner Gregory J Cooney Neil B Ruderman Edward W Kraegen |
author_sort | Amanda E Brandon |
collection | DOAJ |
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. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
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spelling | doaj.art-fe8e9fdd3cf54d85aa3beb4e30f56ed12022-12-22T03:54:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e012195910.1371/journal.pone.0121959Overexpression of SIRT1 in rat skeletal muscle does not alter glucose induced insulin resistance.Amanda E BrandonJennifer Tid-AngLauren E WrightElla StuartEurwin SuryanaNicholas BentleyNigel TurnerGregory J CooneyNeil B RudermanEdward W KraegenSIRT1 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.http://europepmc.org/articles/PMC4370576?pdf=render |
spellingShingle | Amanda E Brandon Jennifer Tid-Ang Lauren E Wright Ella Stuart Eurwin Suryana Nicholas Bentley Nigel Turner Gregory J Cooney Neil B Ruderman Edward W Kraegen Overexpression of SIRT1 in rat skeletal muscle does not alter glucose induced insulin resistance. PLoS ONE |
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 |
url | http://europepmc.org/articles/PMC4370576?pdf=render |
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