Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic β-cells of type 2 diabetic patients
Estimated proinsulin processing activity of prohormone convertase (PC) 1/3 rather than PC2 is decreased in pancreatic β-cells of type 2 diabetic patients
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DOI：
10.1507/endocrj.ej13-0506
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发表时间：
2014-06-20
影响因子：
2
通讯作者：
Ishida, Hitoshi
中科院分区：
文献类型：
--
作者：
Ozawa, Sachihiko;Katsuta, Hidenori;Ishida, Hitoshi
2型糖尿病（T2D）患者由于胰腺β细胞功能障碍而表现出空腹相对高胰岛素原血症。为了阐明这种高胰岛素原血症状态的机制，我们评估了T2D患者内肽酶激素原转化酶（PC）1/3和PC 2的活性。在12名健康志愿者和18名T2D患者中，同时测量空腹血中完整胰岛素原（IPI）、总胰岛素原（t-PI）和C肽水平，并进行静脉内胰高血糖素负荷，以研究从胰腺β细胞释放的循环胰岛素原相关分子的动力学。利用胰岛素原和des-31，32-胰岛素原之间95%的交叉反应性（des-31，32-PI）使用本研究中使用的人胰岛素原放射免疫测定试剂盒，我们使用以下公式估计PC 1/3和PC 2活性：des-31，32-PI =（t-PI-IPI）/0.95; PC 1/3活性= des-31，32-PI/IPI;和PC 2活性= C-肽/des-31，32-PI。T2D患者对胰高血糖素的C肽反应略低。2型糖尿病患者的IPI和IPI/C肽比值显著升高（p
Type 2 diabetic (T2D) patients exhibit fasting relative hyperproinsulinemia owing to pancreatic beta-cell dysfunction. To clarify the mechanism underlying this hyperproinsulinemic state, we evaluated the activities of the endopeptidases prohormone convertase (PC) 1/3 and PC2 in T2D patients. Fasting blood levels of intact proinsulin (IPI), total proinsulin (t-PI) and C-peptide were measured simultaneously, and intravenous glucagon loading was performed to investigate the dynamics of circulating proinsulin-related molecules released from pancreatic beta-cells in 12 healthy volunteers and 18 T2D patients. Taking advantage of the 95% cross-reactivity between proinsulin and des-31,32-proinsulin (des-31,32-PI) with the human proinsulin radioimmunoassay kit used in this study, we estimated PC 1/3 and PC2 activities using the following formulas: des-31,32-PI = (t-PI-IPI)/0.95; PC1/3 activity = des-31,32-PI/IPI; and PC2 activity = C-peptide/des-31,32-PI. C-peptide responses to glucagon were slightly lower among T2D patients. IPI and the IPI/C-peptide ratio were significantly higher in T2D patients (p