title: Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway.
abstract: OBJECTIVE
  It has been reported that irisin regulated exercise-mediated adipocyte browning; however, the systematical effects of irisin on the metabolism of glucose and lipid in diabetes are largely unknown. In the present study, we investigated the role and underlying mechanism of irisin in glucose utilization and lipid metabolism in diabetic mice.
  
  
  METHODS
  A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated.
  
  
  RESULTS
  Irisin improved glucose tolerance and glucose uptake as evidenced by increased (18)F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-β phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid β-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes.
  
  
  CONCLUSIONS
  Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.|Department of Cardiology, The Second Artillery General Hospital of Chinese Peoples's Liberation Army, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Xin
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: D
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.identifier: http://orcid.org/0000-0002-9204-8129
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Pathology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: K
authors.initials: K
authors.lastname: Lian
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: C
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: L
authors.initials: L
authors.lastname: Tao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D001786:Blood Glucose; C571428:FNDC5 protein, mouse; D005227:Fatty Acids; D005353:Fibronectins; D051275:Glucose Transporter Type 4; D055372:AMP-Activated Protein Kinases; D005947:Glucose