Splanchnic and renal metabolism of insulin in human subjects: a dose-response study.

Splanchnic and renal metabolism of insulin in human subjects: a dose-response study.
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人类受试者胰岛素的内脏和肾脏代谢:剂量反应研究。

DOI:
10.1152/ajpendo.1983.244.6.e517
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发表时间:
1983
期刊:
The American journal of physiology
影响因子:
--
通讯作者:
DeFronzo,RA
DeFronzo,RA
中科院分区:
--
文献类型:
--
作者:
Ferrannini,E;Wahren,J;Faber,OK;Felig,P;Binder,C;DeFronzo,RA

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对32名健康受试者进行了胰岛素代谢动力学分析,这些受试者使用葡萄糖-胰岛素钳夹技术获得了高胰岛素血症或高血糖的稳态条件。在基础状态下,内脏床去除了42 +/-2%的胰岛素流入。在分级胰岛素输注并维持血糖正常后,动脉胰岛素水平稳定在35 - 1,430 microU/ml。内脏胰岛素提取在生理胰岛素水平下是恒定的(约60%),但在超生理(大于500 microU/ml)浓度下下降(至29 +/-1%,P小于0.02)。输注胰岛素的代谢清除率在生理浓度范围内基本恒定。高血糖(+125 mg/100 ml)未改变内脏胰岛素提取。基础上,肾脏提取0.04 +/-0.01 mU X min-1 X kg-1或25 +/-5%的动脉胰岛素。肾胰岛素清除率(3.9 +/-0.4 ml X min-1 X kg-1)占胰外胰岛素清除率的80%以上。高血糖(+125 mg/100 ml)对肾胰岛素提取无影响。总之,a)内脏和肾脏胰岛素清除均不依赖于胰岛素水平,并且在生理范围内与血浆胰岛素浓度成比例增加; B)无论输送途径是门静脉还是外周,内脏摄取是从循环中清除胰岛素的主要机制;以及c)肾脏占内脏外胰岛素代谢的大部分。
Kinetic analyses of insulin metabolism were performed in 32 healthy subjects with hepatic-venous or renal-venous catheters, in whom steady-state conditions of hyperinsulinemia or hyperglycemia were achieved with the use of the glucose-insulin clamp technique. In the basal state, the splanchnic bed removed 42 +/- 2% of the insulin influx. After graded insulin infusions with maintenance of euglycemia, stable arterial insulin levels of 35-1,430 microU/ml were attained. Splanchnic insulin extraction was constant (approximately 60%) at physiological insulin levels but fell (to 29 +/- 1%, P less than 0.02) at supraphysiological (greater than 500 microU/ml) concentrations. The metabolic clearance rate of infused insulin was essentially constant within the physiological concentration range. Hyperglycemia (+125 mg/100 ml) did not alter splanchnic insulin extraction. Basally, the kidneys extracted 0.04 +/- 0.01 mU X min-1 X kg-1 or 25 +/- 5% of arterial insulin. Renal insulin clearance (3.9 +/- 0.4 ml X min-1 X kg-1) represented over 80% of the extrasplanchnic insulin clearance. Hyperglycemia (+125 mg/100 ml) had no effect on renal insulin extraction. In conclusion, a) both splanchnic and renal insulin removal are independent of glycemia and increase in proportion to plasma insulin concentration within the physiological range; b) splanchnic uptake is the dominant mechanism of removal of insulin from the circulation whether the route of delivery is portal or peripheral; and c) the kidneys account for the greater part of extrasplanchnic insulin metabolism.
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