Aston Research Centre for Healthy Ageing and School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK.
Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, B4 7ET, UK.
Cardiovasc Diabetol. 2017 Nov 9;16(1):147. doi: 10.1186/s12933-017-0627-2.
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).
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).
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).
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.
鸢尾素是一种主要在运动后由骨骼肌释放的激素，可增加脂肪组织的能量消耗。脂肪细胞在运动后也能释放鸢尾素，作为一种局部脂肪因子，诱导白色脂肪组织呈现出棕色脂肪组织样表型，这表明鸢尾素及其受体可能代表肥胖和肥胖相关糖尿病治疗的新分子靶点。先前的报告提供了关于 2 型糖尿病（T2DM）患者循环鸢尾素水平的相互矛盾的证据。
本研究调查了 79 例 T2DM 个体的血浆鸢尾素浓度，评估了与节段性身体成分、内皮功能障碍标志物和外周血单核细胞端粒长度（TL）的潜在相关性。
与我们之前在健康志愿者中报告的水平相比，这群 T2DM 患者的静息、隔夜禁食血浆鸢尾素水平显著升高（p<0.001）。此外，血浆鸢尾素与体重指数（p=0.04）、体脂肪百分比（p=0.03）、HbA1c（p=0.03）和可溶性 E-选择素（p<0.001）呈正相关。在 T2DM 患者中，血浆鸢尾素与内脏脂肪呈显著负相关（p=0.006）。多元回归分析显示，循环可溶性 E-选择素水平可由血浆鸢尾素预测（p=0.004）。此外，培养的人脐静脉内皮细胞（HUVEC）暴露于 200ng/ml 鸢尾素 4 小时后，E-选择素基因表达显著增加 4 倍（p=0.001 和 p=0.015），条件培养基中可溶性 E-选择素增加 1.8 倍（p<0.05）。
这些数据表明，T2DM 患者血浆鸢尾素升高与肥胖指数相关，鸢尾素可能参与肥胖和 T2DM 伴随的促动脉粥样硬化内皮紊乱。因此，鸢尾素可能是肥胖和心血管糖尿病学领域的一个潜在的新治疗机会。
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