新诊断2型糖尿病患者外周单核细胞ROCK活性与胰岛素抵抗以及胰岛β细胞功能的关系  

Correlation of insulin resistance, pancreatic β-cell function and insulin sensitivity with increased Rho-associated kinase activity in PBMCs in patients with newly diagnosed type 2 diabetes

作　　者：吴斌[1] 高倩[2,3] 楚晓婧[4] 张玫[1] 黄亨建[1] 李贵星[1] 王兰兰[1] 

机构地区：[1]四川大学华西医院实验医学科,四川省成都市610041 [2]卫生部临床检验中心 [3]北京协和医学院研究生院,北京市100730 [4]华中科技大学同济医学院附属同济医院内分泌科,湖北省武汉市430030

出　　处：《世界华人消化杂志》2013年第12期1146-1151,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;No.81101326;四川省科技支撑计划基金资助项目;No.2010SZ0252~~

摘　　要：目的:探讨外周单核细胞Rho相关激酶(Rhoassociated kinases,ROCKs)与胰岛素抵抗、胰岛素细胞功能的关系.方法:研究对象来自于2010-10/2010-12被明确诊断为糖尿病的门诊与体检患者,受试者均为采用空腹血糖检查和高效液相法测定糖化血红蛋白水平.应用Western blot检测新诊断2型糖尿病患者外周单核细胞磷酸化肌球蛋白亚基(phosphor-myosin-binding subunit,p-MBS)与总肌球蛋白亚基(total myosin-binding subunit,t-MBS)蛋白水平,并借由两者的比率反映ROCK活性,分析其与稳态胰岛素评价指数(HOMA-IR)、胰岛素分泌功能指数(HOMA-%B)和胰岛素敏感指数(HOMA-%S)间相关关系.结果:与健康对照组相比,糖尿病组总胆固醇、低密度脂蛋白胆固醇、甘油三酯和空服血糖水平显著升高(5.4±0.8vs4.1±0.6,3.7±0.8vs2.8±0.6,1.7±0.3vs1.1±0.2,8.1±0.9vs5.4±0.4,P<0.001),高密度脂蛋白胆固醇水平则显著降低(0.7±0.1vs1.2±0.1,P<0.001);与健康对照组相比,糖尿病组HOMA-IR显著增高(4.3±1.5vs2.4±1.1,P<0.001),而HOMA-%B与HOMA-%S则显著降低(95.5±21.4vs118.2±16.9,40.2±11.9vs65.9±7.7,P<0.001);糖尿病组与健康组相比ROCK活性显著升高(0.63±0.15vs0.40±0.12,P<0.05);total-MBS、ROCK1和ROCK2表达水平两者间无显著性差异;在糖尿病患者中,ROCK活性与HOMA-IR呈正相关、与HOMA-%B/HOMA-%S则呈负相关.结论:2型糖尿病的胰腺-细胞功能障碍与ROCKs活性密切相关.AIM： To observe the correlation of peripheral mononuclear cells’ Rho-associated kinase activity in peripheral mononuclear cells with HOMA-IR, HOMA-%S and HOMA-%B in patients with newly diagnosed type 2 diabetes （T2D） and healthy subjects. METHODS： For this study, 33 patients with T2D and 33 healthy participants were enrolled and evaluated for clinical and metabolic parameters. Biochemical quantifications and fasting plasma insulin measurement were performed with ROCHE DDP and E601 auto-analyzers, respectively. Rho-associated kinase activity was evaluated in peripheral mononuclear cells by Western blot and defined as the ratio of phosphor myosin-binding subunit on myosin light chain phosphatase to total myosin-binding subunit. HOMA-IR, HOMA-%S and HOMA-%B were calculated with a HOMA2 calculator. RESULTS： The levels of total cholesterol, LDL-cholesterol, triglycerides and fasting glucose were significantly raised （5.4 ± 0.8 vs 4.1 ± 0.6, 3.7 ± 0.8 vs 2.8 ± 0.6, 1.7 ± 0.3 vs 1.1 ± 0.2, 8.1 ± 0.9 vs 5.4 ± 0.4, all P 〈 0.001） and HDL-cholesterol significantly decreased （0.7 ± 0.1 vs 1.2 ± 0.1, P 〈 0.001） in T2D subjects compared with healthy subjects. HOMR-IR significantly increased （4.3 ± 1.5 vs 2.4 ± 1.1, P 〈 0.001） and HOMA-%B and HOMA-%S significantly declined （95.5 ± 21.4 vs 118.2 ± 16.9, 40.2 ± 11.9 vs 65.9 ± 7.7, both P 〈 0.001） in T2D subjects compared with healthy subjects. ROCK activity was more markedly raised in T2D subjects than in healthy subjects （0.63 ± 0.15 vs 0.40 ± 0.12, P 〈 0.05）. The expression of total MBS, ROCK1 and ROCK2 did not differ significantly between the two groups. In diabetic subjects, ROCK activity was positively correlated with HOMA-IR and negatively with HOMA-%B. CONCLUSION： Our findings suggest that pancreatic β-cell dysfunction and the development of type 2 diabetes are associated with ROCK activity in peripheral mononuclear cells.

关 键 词：Rho相关激酶 糖尿病 胰岛素抵抗 相关性 

分 类 号：R587.1[医药卫生—内分泌]