Grodsky G M
J Clin Invest. 1972 Aug;51(8):2047-59. doi: 10.1172/JCI107011.
Phases of insulin release were studied in the perfused pancreas during a variety of glucose stimulation patterns. Patterns included staircase stimulations, constant prolonged single steps, restimulations, and ramp functions. Except at low concentrations, prolonged single steps of glucose elicited early spikes of insulin and a slowly rising second phase. Total insulin in the initial spikes increased with higher glucose concentrations. However, the time-related pattern of these spikes was similar in all cases; ratios of initial secretion rate to total insulin released were constant. Total insulin released in this early phase approximated a sigmoidal function of glucose concentration; mathematical differentiation of this function gave a skewed bell-shaped distribution curve. Staircase stimulations caused insulin to be released as a series of transient spikes which did not correlate with the increment of glucose but rather to the available insulin for a given glucose concentration minus that released in previous steps. The sum of total insulin released as spikes in a staircase series leading to a given glucose concentration was the same as when that concentration was used as a single step. Interrupted prolonged glucose infusions indicated the second phase of insulin release could prime the pancreas and that the first and second phases were interrelated. When glucose was perfused as ramp functions of slow, increasing, concentration, phasic response disappeared.A previous two-compartmental model was expanded to include a threshold or sensitivity distribution hypothesis. This hypothesis proposes that labile insulin is not stored in a homogeneous form but as packets with a bell-shaped distribution of thresholds to glucose. These packets respond quickly when their threshold levels to glucose are reached or exceeded. Data from single step stimulations were utilized for constructing a mathematical model which simulated satisfactorily the various stimulation patterns.
在多种葡萄糖刺激模式下，对灌注胰腺中的胰岛素释放阶段进行了研究。刺激模式包括阶梯式刺激、持续延长的单步刺激、再刺激和斜坡函数。除了在低浓度时，延长的单步葡萄糖刺激会引发胰岛素的早期峰值和缓慢上升的第二阶段。初始峰值中的总胰岛素随着葡萄糖浓度的升高而增加。然而，这些峰值的时间相关模式在所有情况下都是相似的；初始分泌率与释放的总胰岛素的比率是恒定的。在这个早期阶段释放的总胰岛素近似于葡萄糖浓度的S形函数；对该函数进行数学微分得到一条偏态钟形分布曲线。阶梯式刺激导致胰岛素以一系列短暂峰值的形式释放，这些峰值与葡萄糖的增量无关，而是与给定葡萄糖浓度下可用的胰岛素减去前几步释放的胰岛素有关。导致给定葡萄糖浓度的阶梯系列中作为峰值释放的总胰岛素之和与将该浓度用作单步时相同。中断的长时间葡萄糖输注表明胰岛素释放的第二阶段可以使胰腺致敏，并且第一阶段和第二阶段是相互关联的。当葡萄糖以缓慢增加浓度的斜坡函数灌注时，相位反应消失。之前的一个两室模型被扩展以包括阈值或敏感性分布假设。该假设提出，不稳定的胰岛素不是以均匀的形式储存，而是以对葡萄糖阈值呈钟形分布的包的形式储存。当它们对葡萄糖的阈值水平达到或超过时，这些包会迅速做出反应。利用单步刺激的数据构建了一个数学模型，该模型令人满意地模拟了各种刺激模式。
