Mizuno Akira, Arai Hidekazu, Fukaya Makiko, Sato Mitsuyo, Hisami Yamanaka-Okumura, Takeda Eiji, Doi Toshio
Department of Clinical Biology and Medicine, Institute of Health Bioscience, University of Tokushima, Graduate School, Tokushima 770-8503, Japan.
Metabolism. 2007 Jun;56(6):856-62. doi: 10.1016/j.metabol.2007.01.017.
The loss of early-phase insulin secretion is a characteristic feature of type 2 diabetes mellitus. The aim of this study is to examine when impairment of early-phase insulin secretion occurs and whether it can be related to increase in insulin resistance caused by obesity. We developed an analytical method to qualify the early-phase insulin secretion; that is, we measured C-peptide immunoreactivity (CPR) response to a selective increase in blood glucose level in portal vein during oral glucose load under a euglycemic hyperinsulinemic clamp (clamp-OGL). Glucose infusion rate, hepatic glucose uptake, and CPR response during clamp-OGL were measured in 30 subjects with diabetes who were divided into 3 groups based on body mass index, 13 obese subjects with normal glucose tolerance (O-NGT), 10 obese subjects with impaired glucose tolerance (O-IGT), and 15 healthy subjects. Significant increase in CPR levels at 10 minutes in clamp-OGL compared with those at steady state was observed in healthy subjects and in O-NGT; however, those were small or absent in diabetic patients and in O-IGT. The incremental ratio of CPR was not correlated to the makers of insulin resistance. The early-phase insulin secretion is well maintained in O-NGT; however, early-phase insulin secretion has already been disturbed in obese subjects with glucose intolerance.
早期胰岛素分泌缺失是2型糖尿病的一个特征性表现。本研究的目的是探讨早期胰岛素分泌受损发生的时间，以及它是否与肥胖引起的胰岛素抵抗增加有关。我们开发了一种分析方法来评估早期胰岛素分泌；也就是说，在正常血糖高胰岛素钳夹（钳夹-口服葡萄糖耐量试验，clamp-OGL）下口服葡萄糖负荷期间，我们测量门静脉血糖水平选择性升高时的C肽免疫反应性（CPR）反应。对30名糖尿病患者在钳夹-口服葡萄糖耐量试验期间的葡萄糖输注率、肝脏葡萄糖摄取和CPR反应进行了测量，这些患者根据体重指数分为3组，13名糖耐量正常的肥胖受试者（O-NGT）、10名糖耐量受损的肥胖受试者（O-IGT）和15名健康受试者。在健康受试者和O-NGT中，观察到钳夹-口服葡萄糖耐量试验10分钟时的CPR水平与稳态时相比显著升高；然而，在糖尿病患者和O-IGT中，CPR水平升高幅度较小或无升高。CPR的增量比与胰岛素抵抗指标不相关。在O-NGT中早期胰岛素分泌保持良好；然而，糖耐量受损的肥胖受试者的早期胰岛素分泌已经受到干扰。
