title: Sestrin 2 induces autophagy and attenuates insulin resistance by regulating AMPK signaling in C2C12 myotubes.
abstract: Impaired insulin-stimulated glucose uptake in skeletal muscle serves a critical role in the development of insulin resistance (IR), whereas the precise mechanism of the process remains unknown. Recently, the evolutionarily conserved, stress-inducible protein Sestrin2 (Sesn2) has been proposed to play a protective role against obesity-induced IR and diabetes. Activation of Sesn2 may activate AMP-activated protein kinase (AMPK) accompanied by suppression of mammalian target of rapamycin (mTOR), which may ultimately lead to autophagy induction. In view of the potential protective effects of autophagy on the physiological and the pathological regulatory processes via the regulation of energy homeostasis and metabolism, we investigated the effects of Sesn2 on the components of the insulin signaling pathway and insulin-stimulated glucose uptake in palmitate-induced insulin-resistant C2C12 myotubes. We showed that Sesn2 effectively restored the impaired insulin signaling. Moreover, autophagic activity decreased in response to palmitate, whereas Sesn2 significantly reversed the palmitate-suppressed autophagic signaling in this context. Our findings further revealed that Sesn2-induced autophagy contributed to restore the impaired insulin signaling through the activation of AMPK signal. Even in the presence of palmitate, Sesn2 up-regulation maintained insulin sensitivity and glucose metabolism via AMPK-dependent autophagic activation.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huige
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Anatomy and Embryology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Sujuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Hairui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Rehabilitation, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China. Electronic address: lifu@tmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Fu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001343:Autophagy / Q000235:genetics; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010168:Palmitates / Q000378:metabolism; D010544:Peroxidases; D010766:Phosphorylation; D058570:TOR Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D000084622:Sestrins
chemical_list: D055372:AMP-Activated Protein Kinases; D005947:Glucose; D007328:Insulin; D009687:Nuclear Proteins; D010168:Palmitates; D010544:Peroxidases; D058570:TOR Serine-Threonine Kinases; C529380:Sesn2 protein, mouse; D000084622:Sestrins; C546843:mTOR protein, mouse
keywords: AMPK; Autophagy; Insulin signal; Palmitate; Sesn2