Plasma irisin is elevated in type 2 diabetes and is associated with increased E-selectin levels


BACKGROUND: Irisin is a hormone released mainly from skeletal muscle after exercise which increases adipose tissue energy expenditure. Adipocytes can also release irisin after exercise, acting as a local adipokine to induce white adipose tissue to take on a brown adipose tissue-like phenotype, suggesting that irisin and its receptor may represent a novel molecular target for the treatment of obesity and obesity-related diabetes. Previous reports provide conflicting evidence regarding circulating irisin levels in patients with type 2 diabetes (T2DM). METHODS: This study investigated plasma irisin concentrations in 79 T2DM individuals, assessing potential associations with measures of segmental body composition, markers of endothelial dysfunction and peripheral blood mononuclear cell telomere length (TL). RESULTS: Resting, overnight-fasted plasma irisin levels were significantly higher in this group of T2DM patients compared with levels we previously reported in healthy volunteers (p < 0.001). Moreover, plasma irisin displayed a positive correlation with body mass index (p = 0.04), body fat percentage (p = 0.03), HbA1c (p = 0.03) and soluble E-selectin (p < 0.001). A significant negative association was observed between plasma irisin and visceral adiposity (p = 0.006) in T2DM patients. Multiple regression analysis revealed that circulating soluble E-selectin levels could be predicted by plasma irisin (p = 0.004). Additionally, cultured human umbilical vein endothelial cells (HUVEC) exposed to 200 ng/ml irisin for 4 h showed a significant fourfold increase in E-selectin and 2.5-fold increase in ICAM-1 gene expression (p = 0.001 and p = 0.015 respectively), and there was a 1.8-fold increase in soluble E-selectin in conditioned media (p < 0.05). CONCLUSION: These data suggest that elevated plasma irisin in T2DM is associated with indices of adiposity, and that irisin may be involved in pro-atherogenic endothelial disturbances that accompany obesity and T2DM. Accordingly, irisin may constitute a potentially novel therapeutic opportunity in the field of obesity and cardiovascular diabetology.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Engineering & Physical Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
Additional Information: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated. Funding: Aston University and Heart of England NHS Foundation Trust.
Uncontrolled Keywords: Endothelial; Irisin; Soluble E-selectin; Type 2 diabetes
Publication ISSN: 1475-2840
Last Modified: 03 Jun 2024 07:30
Date Deposited: 04 Dec 2017 14:50
Full Text Link:
Related URLs: https://cardiab ... 2933-017-0627-2 (Publisher URL)
PURE Output Type: Article
Published Date: 2017-11-09
Accepted Date: 2017-10-28
Authors: Rana, Karan S
Pararasa, Chathyan
Afzal, Islam
Nagel, David A (ORCID Profile 0000-0002-9055-1775)
Hill, Eric J (ORCID Profile 0000-0002-9419-1500)
Bailey, Clifford J (ORCID Profile 0000-0002-6998-6811)
Griffiths, Helen R
Kyrou, Ioannis (ORCID Profile 0000-0002-6997-3439)
Randeva, Harpal S
Bellary, Srikanth (ORCID Profile 0000-0002-5924-5278)
Brown, James E (ORCID Profile 0000-0002-3504-7373)



Version: Published Version

License: Creative Commons Attribution

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