Boden G, Shimoyama R, Ray T K, Savage R C
Diabetes. 1985 Apr;34(4):342-6. doi: 10.2337/diab.34.4.342.
The effects of anti-insulin receptor antibodies (AIRA) on receptor binding and insulin metabolism were studied in two patients with the type B, severe insulin resistance syndrome. Insulin binding was determined using rat hepatocytes in primary culture and the patient's own red blood cells. Plasma and urinary insulin concentrations and metabolic clearance rates (MCR) were determined in the two patients and in four normal controls in response to infusions of insulin for 60-120 min at rates ranging from 1 to 925 mU/kg/min. In patient 1, basal insulin concentration was 1400 microU/ml. After infusion of 1, 10, and 925 mU/kg/min of insulin it rose to 3800, 5500, and 225,000 microU/ml, respectively. Respective MCRs were 19, 110, and 186 ml/min. In patient 2, basal insulin concentration was 440 microU/ml. After infusion of 1, 10, and 100 mU/kg/min of insulin it rose to 720, 2500, and 18,800 microU/ml, respectively. Respective MCRs were 193, 262, and 294 ml/min. In controls, basal insulin concentration was 4 +/- 0.3 microU/ml. After infusion of 1 and 10 mU/kg/min of insulin, it rose to 82 +/- 17 and 1288 +/- 50 microU/ml. Respective MCRs were 950 and 630 ml/min. These data showed that, in patients with AIRA: (1) insulin metabolism took place at the same rate but at higher insulin concentrations than in normal controls, and (2) MCR increased with rising insulin concentration but remained subnormal even at the highest insulin concentrations. In contrast, MCR in normal controls decreased with increasing insulin concentrations. The data suggest that prevention of insulin binding prevents insulin metabolism at physiologic insulin concentrations and that supraphysiologically elevated insulin concentrations are needed to activate nonreceptor mechanisms.
在两名患有B型严重胰岛素抵抗综合征的患者中，研究了抗胰岛素受体抗体（AIRA）对受体结合及胰岛素代谢的影响。使用原代培养的大鼠肝细胞和患者自身的红细胞来测定胰岛素结合情况。在两名患者和四名正常对照者中，以1至925 mU/kg/min的速率输注胰岛素60 - 120分钟，测定血浆和尿胰岛素浓度以及代谢清除率（MCR）。患者1的基础胰岛素浓度为1400微U/ml。输注1、10和925 mU/kg/min的胰岛素后，其分别升至3800、5500和225,000微U/ml。相应的MCR分别为19、110和186 ml/min。患者2的基础胰岛素浓度为440微U/ml。输注1、10和100 mU/kg/min的胰岛素后，其分别升至720、2500和18,800微U/ml。相应的MCR分别为193、262和294 ml/min。在对照者中，基础胰岛素浓度为4±0.3微U/ml。输注1和10 mU/kg/min的胰岛素后，其分别升至82±17和1288±50微U/ml。相应的MCR分别为950和630 ml/min。这些数据表明，在患有AIRA的患者中：（1）胰岛素代谢速率与正常对照者相同，但发生在更高的胰岛素浓度下；（2）MCR随胰岛素浓度升高而增加，但即使在最高胰岛素浓度下仍低于正常水平。相比之下，正常对照者的MCR随胰岛素浓度升高而降低。数据提示，在生理胰岛素浓度下，阻止胰岛素结合可阻止胰岛素代谢，且需要超生理水平升高的胰岛素浓度来激活非受体机制。
