Teratogenicity of Regular Insulin and Ultralente Insulin in Rats

Abstract

Regular insulin and ultralente insulin were each administered sub-cutaneously (s.c.) in a single dose of 50 IU/body to adult female rats. Both types of insulin lowered blood glucose levels to a considerable degree in the first 1 hr, but they had a different duration of action; the ultralente insulin acted for more than 24 hr while regular insulin was effective for less than 12 hr. These two types of insulin with differently lasting hypoglycemic action were given s.c. in a dose of 50 IU/body/day to pregnant rats at different times during pregnancy. Regular insulin had no teratogenic effect but ultralente insulin specifically produced eye malformations, though not at a high incidence. Determinations of maternal blood glucose levels after s.c. dosing of 50 IU/body/day of ultralente insulin on days 6 - 8 of gestation revealed that most of the malformed fetuses were from among dams with hypoglycemia lasting until 48 hr after the last injection. The results of this study suggest that the teratogenic effect observed is closely related to the duration of maternal hypoglycemia.