Vialettes B, Moulin J P, Gillet T, Bourrely N, Vague P
Presse Med. 1984 Jun 30;13(27):1675-7.
A 60-year old male diabetic patient treated with insulin for 6 years developed ketosis whenever an attempt was made to replace porcine insulin by mixed bovine and porcine insulin. That this resistance was specific to bovine insulin and of immune origin was demonstrated by in vivo and in vitro studies. The in vivo study used a Biostator artificial pancreas: rapid decrease of plasma glucose concentrations was observed under insulin infusion at a constant rate of 200 mU/min with either porcine or semi-synthetic human insulin despite maximum glucose infusion rate (400 mg/min), but not with bovine insulin and a low glucose infusion rate (150 mg/min). In the in vitro study, high levels of anti-insulin antibodies (11.4 m U/ml, Christiansen method) were found in the plasma, and the curves of competitive binding of radiolabelled insulin to the patient's IgG in the presence of unlabelled porcine or bovine insulin showed a 50% decrease of total binding with 0.12 ng/ml of bovine insulin and 25 ng/ml of porcine insulin, suggesting that the affinity of these antibodies for the former was 200 times higher than for the latter.
一名60岁男性糖尿病患者,使用胰岛素治疗6年,每当尝试用牛胰岛素和猪胰岛素混合制剂替代猪胰岛素时,都会发生酮症。体内和体外研究表明,这种抵抗作用对牛胰岛素具有特异性,且源于免疫反应。体内研究使用了生物人工胰腺:在以200 mU/分钟的恒定速率输注胰岛素的情况下,无论输注的是猪胰岛素还是半合成人胰岛素,尽管最大葡萄糖输注速率为400 mg/分钟,但血浆葡萄糖浓度都会迅速下降;而输注牛胰岛素且葡萄糖输注速率较低(150 mg/分钟)时则不会出现这种情况。体外研究发现,患者血浆中存在高水平的抗胰岛素抗体(11.4 m U/ml,克里斯蒂安森方法),在存在未标记的猪胰岛素或牛胰岛素的情况下,放射性标记胰岛素与患者IgG的竞争结合曲线显示,当牛胰岛素浓度为0.12 ng/ml、猪胰岛素浓度为25 ng/ml时,总结合率分别下降了50%,这表明这些抗体对牛胰岛素的亲和力比对猪胰岛素高200倍。