EFFECT OF INSULIN ON THE DISTRIBUTION AND DISPOSITION OF GLUCOSE IN MAN
EFFECT OF INSULIN ON THE DISTRIBUTION AND DISPOSITION OF GLUCOSE IN MAN
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DOI：
10.1172/jci111969
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发表时间：
1985-01-01
影响因子：
15.9
通讯作者：
DEFRONZO, RA
中科院分区：
文献类型：
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作者：
FERRANNINI, E;SMITH, JD;DEFRONZO, RA
了解胰岛素对葡萄糖更新的影响是解释多种代谢情况的关键。然而，关于胰岛素对体内葡萄糖的分布和交换的影响知之甚少。开发了一种生理隔室模型，以描述正常人在基础状态和在葡萄糖高胰岛素血症的稳态条件下的血浆葡萄糖的动力学。在6位健康的志愿者中，将[3-3H]葡萄糖的推注迅速地注入外周静脉，并在很短的时间间隔内监测等离子体放射性的时间顺序，持续150分钟。然后启动了1 mu/min kg胰岛素夹，从而将血浆胰岛素水平提高到高生理高原（.Apprx。100.mu.u/ml）。在90分钟稳定的葡萄糖高胰岛素血症中，给出了[3-3H]葡萄糖的第二个推注，并且在继续夹子的同时，再次将血浆放射性频繁地进行90分钟。在胰岛素前后研究的每个受试者的示踪葡萄糖的血浆消失曲线中清楚地鉴定了三个指数成分。根据严格的统计标准，将基础数据的数据拟合到三室模型。初始分布的区室与等离子池相同（40.+ - 。3 mg/kg）；其他两个隔室的大小相似（91.+ - 。12和96。+ - 。9 mg/kg），但前者与血浆快速交换（平均速率为1.09。+ - 。0.15 min-1 ），而后者交换的速度慢了10倍（0.12。+ - 。0.01 min-1）。葡萄糖周转的基础速率平均为2.15。+ - 。 0.12 mg/min kg，在吸收后状态中葡萄糖的总分布量为26。+ - 。体重的1％。鉴于当前的生理信息，假定较快的交换池代表了人体胰岛素独立的组织，而缓慢交换的池则被吸收到胰岛素依赖性组织中。估计胰岛素非依赖性的葡萄糖摄取（从已发表的数据中）为基础葡萄糖摄取的75％，并且受到限制，以免因葡萄糖高胰岛素血症而变化。当将胰岛素给药期间获得的动力学数据安装到该模型中时，既没有明显更改等离子或快速池的汇率的大小。相比之下，慢速池显着扩展（从96.+ - 。9到190。+ - 。30 mg/kg，p <0.02），同时又与总葡萄糖处置上升了4倍以上（7.96）。 + - 0.85 mg/min kg，p <0.001）。发现慢速池的变化与胰岛素刺激的总葡萄糖更新速率之间存在显着的直接相关性（r = 0.92，p <0.01）。与高血糖无关的高胰岛素血症明显增加了体内可交换的葡萄糖质量，大概反映了胰岛素依赖性组织中游离的，细胞内葡萄糖的积累。
Understanding the influence of insulin on glucose turnover is the key to interpreting a great number of metabolic situations. Little is known, however, about insulin''s effect on the distribution and exchange of glucose in body pools. A physiological compartmental model was developed to describe the kinetics of plasma glucose in normal man in the basal state and under steady-state conditions of euglycemic hyperinsulinemia. A bolus of [3-3H]glucose was rapidly injected into a peripheral vein in 6 healthy volunteers, and the time-course of plasma radioactivity was monitored at very short time intervals for 150 min. A 1-mU/min kg insulin clamp was then started, thereby raising plasma insulin levels to a high physiological plateau (.apprx. 100 .mu.U/ml). After 90 min of stable euglycemic hyperinsulinemia, a 2nd bolus of [3-3H]glucose was given, and plasma radioactivity was again sampled frequently for 90 min more while the clamp was continued. Three exponential components were clearly identified in the plasma disappearance curves of tracer glucose of each subject studied, both before and after insulin. Based on stringent statistical criteria, the data in the basal were fitted to a three-compartment model. The compartmental of initial distribution was identical to the plasma pool (40 .+-. 3 mg/kg); the other 2 compartments had similar size (91 .+-. 12 and 96 .+-. 9 mg/kg), but the former was in rapid exchange with plasma (at an average rate of 1.09 .+-. 0.15 min-1), whereas the latter exchanged 10 times more slowly (0.12 .+-. 0.01 min-1). The basal rate of glucose turnover averaged 2.15 .+-. 0.12 mg/min kg, and the total distribution volume of glucose in the postabsorptive state was 26 .+-. 1% of body weight. In view of current physiological information, it was assumed that the more rapidly exchanging pool represented the insulin-independent tissues of the body, while the slowly exchanging pool was assimilated to the insulin-dependent tissues. Insulin-independent glucose uptake was estimated (from published data) at 75% of basal glucose uptake, and was constrained not to change with euglycemic hyperinsulinemia. When the kinetic data obtained during insulin administration were fitted to this model, neither the size nore the exchange rates of the plasma or the rapid pool were appreciably changed. In contrast, the slow pool was markedly expanded (from 96 .+-. 9 to 190 .+-. 30 mg/kg, P < 0.02) at the same time as total glucose disposal rose 4-fold above basal (to 7.96 .+-. 0.85 mg/min kg, P < 0.001). A significant direct correlation was found to exist between the change in size of the slow pool and the insulin-stimulated rate of total glucose turnover (r = 0.92, P < 0.01). Hyperinsulinemia, independent of hyperglycemia, markedly increases the exchangeable mass of glucose in the body, presumably reflecting the accumulation of free, intracellular glucose in insulin-dependent tissues.