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

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

  • Cardiovasc Diabetol. 2017 Nov 9;16(1):147. doi: 10.1186/s12933-017-0627-2.
Karan S Rana 1 Chathyan Pararasa 1 Islam Afzal 2 David A Nagel 1 Eric J Hill 1 Clifford J Bailey 1 Helen R Griffiths 3 Ioannis Kyrou 2 4 5 Harpal S Randeva 2 4 5 Srikanth Bellary 1 6 James E Brown 7 8
Affiliations

Affiliations

  • 1 Aston Research Centre for Healthy Ageing and School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK.
  • 2 Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, B4 7ET, UK.
  • 3 Faculty of Health and Medical Sciences, University of Surrey, Guildford, GU2 7XH, UK.
  • 4 Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals Coventry and Warwickshire NHS Trust, Coventry, CV2 2DX, UK.
  • 5 Translational & Experimental Medicine, Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
  • 6 Department of Diabetes and Endocrinology, Diabetes Outpatient Clinics at the Heart of England NHS Foundation Trust, Birmingham, B9 5SS, UK.
  • 7 Aston Research Centre for Healthy Ageing and School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK. j.e.p.brown@aston.ac.uk.
  • 8 Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, B4 7ET, UK. j.e.p.brown@aston.ac.uk.
Abstract

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.

Keywords

Endothelial; Irisin; Soluble E-selectin; Type 2 diabetes.

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