Wentzel P, Eriksson UJ. Insulin treatment fails to abolish the teratogenic potential of serum from diabetic rats. Eur J Endocrinol 1996;134:459–66. ISSN 0804–4643
Maternal diabetes during pregnancy constitutes an increased risk for congenital malformations in the offspring. Previous studies have identified several serum components with teratogenic activity, e.g. glucose and β-hydroxybutyrate, but have also suggested that the teratogenic influence of the diabetic environment on the developing embryo is multifactorial and may depend upon changed concentrations of several maternal metabolites. In the present investigation we aimed to assess the teratological impact of small, concomitant alterations in a series of metabolites, particularly those not previously identified as teratogens. We thus investigated the influence of a mild diabetic environment by culturing gestational day-9 rat embryos in serum from insulin-treated diabetic rats for 48 h in vitro, and compared the embryonic outcome with that obtained after culture in normal serum and in serum from manifestly diabetic rats without insulin treatment. The glucose concentration was adjusted to 10 or 30 mmol/l in the cultures, and the embryos were evaluated with respect to crown–rump length, protein and DNA content, number of somites and malformation score (comparing major, minor or no malformations). We found that increased glucose levels caused embryonic maldevelopment in both normal and diabetic serum, and that despite normalization of the diabetic state, the serum from the insulin-treated diabetic rats caused more growth retardation than the nondiabetic control serum. The normalized diabetic serum was also more teratogenic than the normal serum at the low glucose concentration, whereas the serum from the manifestly diabetic rats tended to cause more dysmorphogenesis at 30 mmol/l glucose than both the normal and normalized diabetic serum. The results suggest that the teratogenicity of maternal serum in diabetic pregnancy is not mediated exclusively by increased concentrations of glucose and ketone bodies. The efforts to diminish the teratogenic effects of a diabetic environment should therefore include normalization of a multitude of serum factors, including glucose and ketone bodies.
Parri Wentzel, Department of Medical Cell Biology, University of Uppsala, Biomedicum, PO Box 571, S-751 23 Uppsala, Sweden
The effect of insulin treatment on the smooth muscle contractility and endothelium-dependent relaxation of aortae from progressed STZ-induced diabetic rats