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

ABSTRACT

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 HbA1c 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 HbA1c concentration in type 2 diabetes (ß=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.