Effects of D-glucose and beta-hydroxybutyric acid on the in vitro development of (pre)chondrocytes from embryos of normal and diabetic rats.

In order to elucidate cellular mechanisms causing skeletal malformations in offspring of diabetic rats we studied the incorporation of thymidine and sulphate into embryonic (pre)chondrocytes exposed to increased levels of D-glucose and beta-hydroxybutyric acid for six days in vitro. The (pre)chondrocytes were prepared from embryos of normal or diabetic rats of a malformation-prone strain or from embryos of normal rats of a non-malformation-prone strain. Diabetic female rats of the former strain are known to produce a high proportion of offspring with mandibular and lumbosacral malformations. Increased beta-hydroxybutyric acid caused decreased thymidine incorporation in all types of chondrocytes, and decreased sulphate incorporation in limb bud cells from embryos of normal rats from both strains. Elevated D-glucose levels yielded a slight decrease in thymidine incorporation in mandibular arch cells from embryos of normal rats of the malformation-prone strain, and a marked decrease of both sulphate and thymidine incorporation in mandibular arch cells from embryos of diabetic rats of this strain. The observations suggest that elevated levels of D-glucose or beta-hydroxybutyric acid are able to inhibit the differentiation and growth of (pre)-chondrocytes and illustrate a selective sensitivity of mandibular arch (pre)chondrocytes to a diabetic environment. The data are compatible with the view that both D-glucose and beta-hydroxybutyric acid may cause aberrations in the development of rat mandibular arch chondrocytes, suggesting a role for these compounds in diabetic teratogenesis.