Abdel-Wahab Y H, O'Harte F P, Boyd A C, Barnett C R, Flatt P R
School of Biomedical Sciences, University of Ulster, UK.
Acta Diabetol. 1997 Dec;34(4):265-70. doi: 10.1007/s005920050086.
Bovine insulin was glycated by in vitro incubation with 20-220 mM D-glucose for 1-48 h. The percentage of glycation was dependent on time, glucose concentration, temperature and pH, attaining values up to 28%. Glucose-lowering activities of glycated and control (non-glycated) insulin preparations were assessed in mice by intraperitoneal injection in a 39% (w/v) glucose solution (2 g/kg body weight) at doses of 0.05 and 0.25 units/kg body weight. Injection of glucose alone significantly (P < 0.001) increased plasma glucose concentrations at 30 min. Simultaneous administration of non-glycated insulin with glucose significantly decreased the 30-min glycaemic excursion (P < 0.001) in a dose-dependent manner. Glycated insulin exhibited a significant reduction (P < 0.001) in glucose-lowering activity under these conditions. The relationship between the extent of insulin glycation and glucose-lowering activity at 0.25 units/kg was assessed using five different insulin preparations glycated between 6%-28%. The insulin-induced decrease in plasma glucose at 30 min was inversely related to the extent of glycation (r = 0.99). Glycated insulin (10(-8) and 10(-6) M) also exhibited a significantly reduced (P < 0.05) ability to stimulate glucose oxidation in isolated mouse diaphragm muscle compared with non-glycated insulin. These data indicate that glycated insulin exhibits impaired biological activity which may contribute to glucose intolerance in diabetes. Further studies are required to determine if glycation of insulin occurs in man and if this process contributes to the pathogenesis of diabetes.
通过与20 - 220 mM D - 葡萄糖在体外孵育1 - 48小时使牛胰岛素糖基化。糖基化百分比取决于时间、葡萄糖浓度、温度和pH值，可达28%。通过腹腔注射39%（w/v）葡萄糖溶液（2 g/kg体重），以0.05和0.25单位/kg体重的剂量，在小鼠中评估糖基化胰岛素制剂和对照（非糖基化）胰岛素制剂的降糖活性。单独注射葡萄糖在30分钟时显著（P < 0.001）提高血浆葡萄糖浓度。非糖基化胰岛素与葡萄糖同时给药以剂量依赖方式显著降低30分钟血糖波动（P < 0.001）。在这些条件下，糖基化胰岛素的降糖活性显著降低（P < 0.001）。使用五种糖基化程度在6% - 28%之间的不同胰岛素制剂评估了0.25单位/kg时胰岛素糖基化程度与降糖活性之间的关系。胰岛素诱导的30分钟时血浆葡萄糖降低与糖基化程度呈负相关（r = 0.99）。与非糖基化胰岛素相比，糖基化胰岛素（10(-8)和10(-6) M）在分离的小鼠膈肌中刺激葡萄糖氧化的能力也显著降低（P < 0.05）。这些数据表明，糖基化胰岛素表现出受损的生物活性，这可能导致糖尿病患者的葡萄糖不耐受。需要进一步研究以确定胰岛素糖基化在人类中是否发生以及该过程是否有助于糖尿病的发病机制。
