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Overexpression of SIRT1 in rat skeletal muscle does not alter glucose induced insulin resistance


SIRT1 is a NAD+-dependent deacetylase enzyme thought to regulate metabolic pathways within cells in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 affect markers of muscle mitochondrial content and also determined if SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. Male Wistar rats were electroporated with either SIRT1 or a deacetylase inactive mutant of SIRT1 (H363Y) into one tibialis cranialis (TC) muscle with an empty vector in the other TC serving as a control. Animals then immediately underwent cannulation surgery. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours this protocol generates 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 have little impact on mitochondrial function and that SIRT1 is not involved in the development of muscle insulin resistance that occurs after a hyperglycaemic insult.

Type Journal
Authors Brandon, A. E.; Tid-Ang, J.; Wright, L. E.; Stuart, E.; Suryana, E.; Bentley, N.; Turner, N.; Cooney, G. J.; Ruderman, N. B.; Kraegen, E. W.;
Publisher Name PLoS One
Published Date 2015-02-01
Published Volume 10
Published Issue 3
Published Pages e0121959
Status Published in-print
DOI 10.1371/journal.pone.0121959
URL link to publisher's version
OpenAccess link to author's accepted manuscript version