Sundsten Tea, Zethelius Björn, Berne Christian, Bergsten Peter
Department of Medical Cell Biology, Uppsala University, SE-751 23 Uppsala, Sweden.
Clin Sci (Lond). 2008 Apr;114(7):499-507. doi: 10.1042/CS20070323.
Circulating proteins contribute to the pathogenesis of T2DM (Type 2 diabetes mellitus) in various ways. The aim of the present study was to investigate variations in plasma protein levels in subjects with T2DM and differences in beta-cell function, characterized by the EIR (early insulin response), and to compare these protein levels with those observed in individuals with NGT (normal glucose tolerance). Ten subjects with NGT+high EIR, ten with T2DM+high EIR, and ten with T2DM+low EIR were selected from the community-based ULSAM (Uppsala Longitudinal Study of Adult Men) cohort. Plasma protein profiling was performed using SELDI-TOF (surface-enhanced laser-desorption ionization-time-of-flight) MS. In total, nine plasma proteins differed between the three study groups (P<0.05, as determined by ANOVA). The levels of two forms of transthyretin, haemoglobin alpha-chain and haemoglobin beta-chain were decreased in plasma from subjects with T2DM compared with subjects with NGT, irrespective of the EIR of the subjects. Apolipoprotein H was decreased in plasma from individuals with T2DM+high EIR compared with subjects with NGT. Four additional unidentified plasma proteins also varied in different ways between the experimental groups. In conclusion, the proteins detected in the present study may be related to the development of beta-cell dysfunction.
循环蛋白以多种方式参与2型糖尿病（T2DM）的发病机制。本研究旨在调查T2DM患者血浆蛋白水平的变化以及以早期胰岛素反应（EIR）为特征的β细胞功能差异，并将这些蛋白水平与糖耐量正常（NGT）个体的蛋白水平进行比较。从基于社区的ULSAM（乌普萨拉成年男性纵向研究）队列中选取了10名NGT+高EIR患者、10名T2DM+高EIR患者和10名T2DM+低EIR患者。使用表面增强激光解吸电离飞行时间（SELDI-TOF）质谱进行血浆蛋白谱分析。三个研究组之间共有9种血浆蛋白存在差异（经方差分析，P<0.05）。与NGT患者相比，T2DM患者血浆中两种形式的转甲状腺素蛋白、血红蛋白α链和血红蛋白β链水平降低，与患者的EIR无关。与NGT患者相比，T2DM+高EIR个体血浆中的载脂蛋白H降低。另外还有4种未鉴定的血浆蛋白在各实验组之间也有不同程度的变化。总之，本研究中检测到的蛋白可能与β细胞功能障碍的发生有关。
