Lindsay J R, McKillop A M, Mooney M H, O'Harte F P M, Flatt P R, Bell P M
Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, BT12 6BA Belfast, UK.
Diabetes Res Clin Pract. 2003 Sep;61(3):167-73. doi: 10.1016/s0168-8227(03)00107-4.
Glycation of insulin has been demonstrated within pancreatic beta-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes.
Ten patients (5 M/5 F, age 57.8+/-1.9 years, HbA(1c) 7.6+/-0.5%, fasting plasma glucose 9.4+/-1.2 mmol/l, creatinine 81.6+/-4.5 microM/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min.
Plasma glucose and glycated insulin responses were reduced by 9% (P=0.005) and 38% (P=0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P=0.005) and 25% (P=0.007) by nateglinide.
Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the antihyperglycaemic action of nateglinide.
已证实在胰腺β细胞内存在胰岛素糖基化，其导致的生物活性受损可能会导致糖尿病患者出现胰岛素抵抗。我们使用一种新型放射免疫分析法来评估那格列奈对2型糖尿病患者糖化胰岛素血浆浓度及葡萄糖耐量的影响。
10名患者（5名男性/5名女性，年龄57.8±1.9岁，糖化血红蛋白7.6±0.5%，空腹血糖9.4±1.2 mmol/L，肌酐81.6±4.5 μmol/L）采用随机、单盲、交叉设计，在口服75 g葡萄糖前10分钟分别服用120 mg那格列奈或安慰剂，间隔1周。在225分钟内采集血样检测糖化胰岛素、葡萄糖、胰岛素和C肽。
与安慰剂相比，那格列奈治疗后血浆葡萄糖和糖化胰岛素反应分别降低了9%（P = 0.005）和38%（P = 0.047）。那格列奈使胰岛素和C肽相应的曲线下面积测量值分别增加了36%（P = 0.005）和25%（P = 0.007）。
2型糖尿病患者中，胰岛素促分泌剂那格列奈可降低糖化胰岛素水平，从而使天然胰岛素优先释放。由于糖化胰岛素的生物活性受损，糖化胰岛素释放减少可能有助于那格列奈的降糖作用。
