title: Overexpression of SIRT1 in rat skeletal muscle does not alter glucose induced insulin resistance.
abstract: 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.
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia.
authors: Amanda E
authors: AE
authors: Brandon
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia.
authors: Jennifer
authors: J
authors: Tid-Ang
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia.
authors: Lauren E
authors: LE
authors: Wright
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia.
authors: Ella
authors: E
authors: Stuart
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia.
authors: Eurwin
authors: E
authors: Suryana
authors: UNSW Medicine, University of New South Wales, Sydney, Australia.
authors: Nicholas
authors: N
authors: Bentley
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia; UNSW Medicine, University of New South Wales, Sydney, Australia.
authors: Nigel
authors: N
authors: Turner
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia; UNSW Medicine, University of New South Wales, Sydney, Australia.
authors: Gregory J
authors: GJ
authors: Cooney
authors: Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors: Neil B
authors: NB
authors: Ruderman
authors: Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW, 2010, Australia; UNSW Medicine, University of New South Wales, Sydney, Australia.
authors: Edward W
authors: EW
authors: Kraegen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D018274:Electroporation; D005947:Glucose / Q000494:pharmacology*; D006943:Hyperglycemia / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000502:physiology*
chemical_list: D001786:Blood Glucose; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose