insulin--desoctapeptide- and Fetal-Death

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.

Topics: Abnormalities, Drug-Induced; Animals; Chick Embryo; Embryonic and Fetal Development; Female; Fetal Death; Glucose; Insulin; Insulin-Like Growth Factor II; Peptides; Pregnancy; Proinsulin; Receptor, Insulin; Receptors, Cell Surface; Receptors, Somatomedin