title: Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses.
abstract: Vascular complications are the major causes of death in patients with diabetes, and endothelial dysfunction is the earliest event in vascular complications of diabetes. It has been reported that plasma irisin level is significantly reduced in patients with type 2 diabetic patients. The present study aimed to investigate whether irisin improved endothelial function in type 2 diabetes as well as the underlying mechanisms. The type 2 diabetes model was established by feeding C57BL/6 mice with high-fat diet. The type 2 diabetic mice exhibited reduced serum irisin level and impaired endothelial function. Irisin treatment (0.5 mg/kg/d) for two weeks improved vascular function based on the evaluation of endothelium-dependent vasorelaxation and p-VASP levels. To investigate the direct endothelial protective effects of irisin, diabetic aortic segments were incubated with irisin (1 μg/ml) ex vivo. Exposure to irisin improved endothelium-dependent vasorelaxation of diabetic aortas. Mechanically, the diabetic aortic segments exhibited increased oxidative/nitrative stresses. Irisin reduced the diabetes-induced oxidative/nitrative stresses evidenced by reducing overproduction of superoxide and peroxynitrite, and down-regulation of iNOS and gp91(phox). To further investigate the protective effects of irisin on endothelial cells and the underlying mechanisms, human umbilical vein endothelial cells (HUVECs) cultured in high-glucose/high-fat (HG/HF) medium were pre-incubated with irisin. Irisin (1 μg/ml) reduced the oxidative/nitrative stresses and apoptosis induced by HG/HF in HUVECs probably via inhibiting activation of PKC-β/NADPH oxidase and NF-κB/iNOS pathways. Taken together, irisin alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses through inhibiting signaling pathways implicating PKC-β/NADPH oxidase and NF-κB/iNOS, suggesting that irisin may be a promising molecule for the treatment of vascular complications of diabetes.
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Physical Examination Team for Recruiting Pilots, Air Force General Hospital of People's Liberation Army, Beijing 100142, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jinglong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Xin
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fuyang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Lian
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA 19170, USA.
authors.forename: Xinliang
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; Department of Physiology, Fourth Military Medical University, Xi'an 710032, China. Electronic address: liuyimeishan@hotmail.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address: lingtao2006@gmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: Tao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000473:pathology; D059305:Diet, High-Fat; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins / Q000008:administration & dosage / Q000097:blood*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D014664:Vasodilation / Q000187:drug effects* / Q000235:genetics
chemical_list: D000975:Antioxidants; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D016328:NF-kappa B
keywords: Endothelium; Irisin; Oxidative/nitrative stress; Type 2 diabetes