Effects of low insulin levels on rat embryonic growth and development.

The risk of congenital abnormality in diabetic pregnancy is about four times that for the normal population. Past clinical studies have suggested hyperglycemia and hyperketonemia as the factors responsible for these abnormalities, with no reference to the possible effects of low insulin levels. We examine the effect of hypoinsulinemia on rat embryonic growth and development in culture while normal glucose levels are maintained. With anti-insulin antibody bound to an affinity column containing cyanogen bromide-activated Sepharose 4B beads, insulin was selectively removed from the homologous culture serum eluted down the column. A culture of rat embryos from the early head-fold stage for 50 h in insulin-depleted normoglycemic homologous serum (insulin levels 0.055-0.18 ng/ml) showed retardation of growth and development when compared with control embryos. Adding physiological amounts (10 ng/ml) of insulin back into the insulin-depleted serum subsequently restored growth level to that of control embryos. We conclude that low insulin levels, encountered in newly diagnosed diabetic pregnancy, may be instrumental in increasing the risk of congenital abnormalities.