Enhanced Rho-kinase activity: Pathophysiological relevance in type 2 diabetes

Enhanced Rho-kinase activity: Pathophysiological relevance in type 2 diabetes
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Rho 激酶活性增强:2 型糖尿病的病理生理学相关性

DOI:
10.1016/j.cca.2016.09.003
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发表时间:
2016-11-01
影响因子:
5
通讯作者:
Wang, Dao Wen
Wang, Dao Wen
中科院分区:
医学3区
文献类型:
--
作者:
Liu, Lei;Tan, Lun;Wang, Dao Wen

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背景资料:越来越多的证据表明Rho相关激酶(ROCK)参与了胰岛素抵抗和糖尿病的发病机制。然而,糖尿病患者中ROCK活性的临床证据很少。我们确定是否ROCK活性是系统增强2型糖尿病患者和与其他组件的diabetes.Methods:78名志愿者,包括41例2型糖尿病患者和37名对照组,参加了这项研究。收集空腹血液样品以测量循环白细胞中的ROCK活性,通过磷酸化/总肌球蛋白结合亚基(MBS)(ROCK的直接下游靶标)的比率来确定。与对照组相比,2型糖尿病患者的ROCK活性显著升高(磷酸化/总MBS比率0.80 +/-0.10对比0.72 +/-0.08,P < 0.01)。2型糖尿病患者ROCK活性与HbA(1c)浓度呈独立正相关(r = 0.40,P = 0.01)。多元回归分析显示,2型糖尿病患者ROCK活性与HbA(1c)浓度呈显著正相关(β = 0.03,P = 0.04)。结论:2型糖尿病患者ROCK活性明显增高,ROCK活性增高可能反映了疾病的进展。(C)© 2016 Elsevier B. V.版权所有。
Background: Accumulating evidence indicates that Rho-associated kinase (ROCK) has been involved in the pathogenesis of insulin resistance and diabetes. However, little clinical evidence for ROCK activity in diabetic patients is available. We determined whether ROCK activity is systemically enhanced in type 2 diabetic patients and associated with other components of diabetes.Methods: Seventy-eight volunteers, including 41 type 2 diabetic patients and 37 control subjects, were participated in this study. Fasting blood samples were collected to measure ROCK activity in circulating leukocyte, determined by the ratio of phosphorylation/total myosin-binding subunit (MBS), a direct downstream target of ROCK.Results: Compared with the control subjects, ROCK activity was significantly increased in type 2 diabetic patients (phosphorylation/total MBS ratio 0.80 +/- 0.10 vs. 0.72 +/- 0.08, P < 0.01). An independent positive correlation was found between ROCK activity and HbA(1c) concentration in type 2 diabetic patients but not in control subjects (r = 0.40, P = 0.01). In multiple regression analysis, ROCK activity remains associated significantly in a positive manner with HbA(1c) concentration in type 2 diabetes (beta = 0.03, P = 0.04).Conclusions: These findings demonstrated that ROCK activity is significantly increased in type 2 diabetic patients and enhanced ROCK activity may reflect the progression of disease. (C) 2016 Elsevier B.V. All rights reserved.