de Pablo F, Hernández E, Collía F, Gómez J A
Diabetologia. 1985 May;28(5):308-13. doi: 10.1007/BF00271691.
The teratogenic effect of insulin in early vertebrate embryos is controversial and the mechanisms involved are unknown. We studied the effects of pharmacological doses of insulin in chick embryos during the period of differentiation. We compared the effects of insulin with two proinsulins, desoctapeptide-insulin and multiplication-stimulating activity, peptides that have little insulin-like metabolic activity while they have significant growth effects. Chick embryos at 46 h of development were injected with the different peptides. At 96 h the mortality and abnormal growth elicited by the peptides were dose-dependent. Considering the indices of lethality (LD50) and affected embryos (ED50) as 100% for insulin, proinsulin was 59-66% as potent as insulin, desoctapeptide-insulin 2-6% and multiplication-stimulating activity 176-204%. In the surviving embryos, insulin (5 micrograms, decreased DNA, RNA and protein content by 49%, 40% and 48% respectively compared with controls. The effects of insulin were not corrected by simultaneous glucose injections. These data suggest that insulin, at pharmacological doses, interferes with embryo development through a non-metabolic pathway, probably via a growth-type receptor.
胰岛素在早期脊椎动物胚胎中的致畸作用存在争议，其涉及的机制尚不清楚。我们研究了药理学剂量的胰岛素在鸡胚分化期的作用。我们将胰岛素的作用与两种胰岛素原、去八肽胰岛素和促增殖活性肽进行了比较，这些肽几乎没有胰岛素样代谢活性，但具有显著的生长效应。将发育46小时的鸡胚注射不同的肽。在96小时时，肽引起的死亡率和异常生长呈剂量依赖性。以胰岛素的致死指数（LD50）和受影响胚胎指数（ED50）为100%，胰岛素原的效力为胰岛素的59 - 66%，去八肽胰岛素为2 - 6%，促增殖活性肽为176 - 204%。在存活的胚胎中，胰岛素（5微克）与对照组相比，DNA、RNA和蛋白质含量分别降低了49%、40%和48%。同时注射葡萄糖并不能纠正胰岛素的作用。这些数据表明，药理学剂量的胰岛素通过非代谢途径干扰胚胎发育，可能是通过一种生长型受体。
