title: SIRT1 attenuates high glucose-induced insulin resistance via reducing mitochondrial dysfunction in skeletal muscle cells.
abstract: Insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes mellitus (T2DM). Sustained high glucose is an important extracellular environment that induces insulin resistance. Acquired insulin resistance is associated with reduced insulin-stimulated mitochondrial activity as a result of increased mitochondrial dysfunction. Silent information regulator 1 (SIRT1) is one member of the SIRT2 (Sir2)-like family of proteins involved in glucose homeostasis and insulin secretion in mammals. Although SIRT1 has a therapeutic effect on metabolic deterioration in insulin resistance, it is still not clear how SIRT1 is involved in the development of insulin resistance. Here, we demonstrate that pcDNA3.1 vector-mediated overexpression of SIRT1 attenuates insulin resistance in the high glucose-induced insulin-resistant skeleton muscle cells. These beneficial effects were associated with ameliorated mitochondrial dysfunction. Further studies have demonstrated that SIRT1 restores mitochondrial complex I activity leading to decreased oxidative stress and mitochondrial dysfunction. Furthermore, SIRT1 significantly elevated the level of another SIRT which is named SIRT3, and SIRT3 siRNA-suppressed SIRT1-induced mitochondria complex activity increments. Taken together, these results showed that SIRT1 improves insulin sensitivity via the amelioration of mitochondrial dysfunction, and this is achieved through the SIRT1-SIRT3-mitochondrial complex I pathway.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Hao-Hao
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ma
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wu
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Peng-Yu
authors.initials: PY
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Shao
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Division of Vasculitis, Guancheng Traditional Chinese Medical Hospital, Zhengzhou 450016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China hyqingj@zzu.edu.cn.
authors.forename: Gui-Jun
authors.initials: GJ
authors.lastname: Qin
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D005947:Glucose / Q000008:administration & dosage*; D007333:Insulin Resistance; D051379:Mice; D008931:Mitochondria, Muscle / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000502:physiology*
chemical_list: D017931:DNA Primers; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D005947:Glucose
keywords: Insulin resistance; high glucose; mitochondrial dysfunction; silent information regulator 1; skeletal muscle cells