Ratzmann K P, Schulz B, Witt S, Heinke P, Ziegler M
Endokrinologie. 1981 Oct;78(1):89-98.
We have studied changes in the sensitivity of the early insulin response to glucose by means of an intravenous pulse-stimulation of 1.0 g, 2.5 g and 5.0 glucose at intervals of 30 min in 24 non-obese healthy controls without a family history of diabetes and in obese subjects with normal (n = 7) and pathological carbohydrate tolerance (n = 23). All subjects were characterized regarding carbohydrate tolerance (CHT) by using a 2 h-glucose infusion test (GIT; 12 mg/kg/min), primed by an initial injection of 0.33 g/kg glucose. Compared with controls the early insulin response (delta IRI-area 0-5 min) during GIT was slightly increased in obesity with normal CHT and it was significantly reduced in obesity with pathological CHT. With regard to the late insulin response phase (delta IRI-area 30-120 min) both obese groups were characterized by a significant hyperinsulinemia. During staircase glucose stimulation a dose-dependent significant increase of the maximal IRI-response was observed in controls whereas this strong relationship was lacking in the two obese groups. The dose-response curve in obesity with normal CHT was displaced toward the left of the control curve whereas a right shift was found in obesity with pathological CHT. There was a significant correlation between early insulin response during GIT and maximal insulin response revealed by staircase glucose stimulation in obese subjects with pathological CHT. No close relationship of this type could be detected in the other groups so far studied. Our findings suggest an increased sensitivity of the beta-cells to glucose in the hyperinsulinemia stages of obesity with normal CHT. In contrast to this, a reduced sensitivity of the early insulin response to glucose is suggested in obesity with pathological CHT. A staircase glucose stimulation seems to be a useful tool in studying the early insulin response to glucose.
我们通过对24名无糖尿病家族史的非肥胖健康对照者以及7名糖耐量正常和23名糖耐量异常的肥胖受试者，每隔30分钟静脉注射1.0g、2.5g和5.0g葡萄糖进行脉冲刺激，研究了早期胰岛素对葡萄糖反应敏感性的变化。所有受试者均采用2小时葡萄糖输注试验（GIT；12mg/kg/min），初始注射0.33g/kg葡萄糖进行负荷，以评估糖耐量（CHT）。与对照组相比，糖耐量正常的肥胖者在GIT期间早期胰岛素反应（0-5分钟胰岛素释放增量面积）略有增加，而糖耐量异常的肥胖者则显著降低。在晚期胰岛素反应阶段（30-120分钟胰岛素释放增量面积），两个肥胖组均表现为显著的高胰岛素血症。在阶梯式葡萄糖刺激过程中，对照组观察到最大胰岛素释放反应呈剂量依赖性显著增加，而两个肥胖组则缺乏这种强相关性。糖耐量正常的肥胖者的剂量反应曲线向对照曲线左侧偏移，而糖耐量异常的肥胖者则向右偏移。在糖耐量异常的肥胖受试者中，GIT期间的早期胰岛素反应与阶梯式葡萄糖刺激显示的最大胰岛素反应之间存在显著相关性。在迄今为止研究的其他组中未发现这种密切关系。我们的研究结果表明，在糖耐量正常的肥胖高胰岛素血症阶段，β细胞对葡萄糖的敏感性增加。与此相反，糖耐量异常的肥胖者提示早期胰岛素对葡萄糖的反应敏感性降低。阶梯式葡萄糖刺激似乎是研究早期胰岛素对葡萄糖反应的有用工具。
