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

Abstract

BackgroundIrisin 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).MethodsThis 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).ResultsResting, 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).ConclusionThese 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.

Several Circulating Biomarkers for PCOS Diagnosis

“…Irisin has been identified as a novel myokine, which has been reported to be associated with the browning of white adipose tissue (WAT) and regulating energy balance, etc., [11]. Betatrophin has also been found to regulate β-cell proliferation, glucose/lipid homeostasis and autophagic flux [20]. Previous studies have shown that circulating ZAG, Irisin and Betatrophin concentrations were significantly reduced or elevated in patients with T2DM or PCOS, respectively, and were associated with IR [10][11][12][20][21][22].…”

“…Betatrophin has also been found to regulate β-cell proliferation, glucose/lipid homeostasis and autophagic flux [20]. Previous studies have shown that circulating ZAG, Irisin and Betatrophin concentrations were significantly reduced or elevated in patients with T2DM or PCOS, respectively, and were associated with IR [10][11][12][20][21][22]. In addition, a recent meta-analysis and other populations had indicated that serum irisin concentration in PCOS women were higher than that in healthy women, this elevaluation could be partly attributed to the BMI in PCOS patients [23][24][25][26].…”

“…In PCOS patients, circulating ZAG levels were reported to be consistently reduced [10,27,28]. However, the relationship between circulating betatrophin levels and PCOS is controversial and the studies in the literature are inconsistent [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. Growing evidence indicates that these cytokines have some roles in the pathogenesis of T2DM and PCOS, and are also involved in IR development.…”

Perivascular adipose tissue in cardiovascular diseases – an update

“…This paracrine adipokine induces the WAT to adopt a brown adipose tissue-like phenotype, but, concomitantly, it may lead to endothelial dysfunction and atheromatous lesions in patients with diabetes. Hence, irisin and its receptor may be new therapeutic targets in diabetes mellitus and obesity (40).…”

Circulating Irisin and esRAGE as Early Biomarkers of Decline of Metabolic Health

“…Up until now, the optimal irisin level in human has not been established, and controversial results about its levels in different pathological conditions have been observed. In fact, both decreased and increased irisin levels have been observed in DM, insulin resistance and metabolic syndrome [19][20][21][22][23]. If, from one side, irisin reduction might lead to some metabolic changes involved in the onset and progression of a disease, on the other side its up-regulation could be a consequence of an "irisin resistance" state and therefore an attempt to maximize the anti-obesity, anti-hyperglycemic and healthy effects of the molecule.…”