The effects of induced type-I diabetes on developmental regulation of insulin & insulin like growth factor-1 (IGF-1) receptors in the cerebellum of rat neonates

Abstract

Diabetes during pregnancy impairs brain development in offspring, leading to behavioral problems, motor dysfunction and learning deficits. Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. Aim of the present study was to examine the effects of maternal diabetes on insulin receptor (InsR) and IGF-1 receptor (IGF-1R) expression in the developing rat cerebellum. Wistar female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was killed at P0, P7, and P14, an active neurogenesis period in brain development equivalent to the third trimester in human. The expression of InsR and IGF-1R in cerebelli was evaluated using real-time PCR and western blot analysis. We found a significant upregulation of both IGF-1R and InsR transcripts in cerebellum of pups born to diabetic mothers at P0, compared to controls. However, at the same time point, the results of western blot analysis revealed only a slight change in their protein levels. In contrast to InsR, which does not show any difference, there was a markedly reduction in cerebellar expression of IGF-1R mRNA and protein level in the diabetic group of newborns at P7. Moreover, 2 weeks after birth, mRNA expression and protein levels of both InsR and IGF-1R in cerebellum of the diabetic group was significantly downregulated. Compared to controls, we did not find any difference in cerebellar InsR or IGF-1R mRNA and protein levels in the insulin treated group. The present study revealed that diabetes during pregnancy strongly influences the regulation of both InsR and IGF-1R in the developing cerebellum. Furthermore, optimal maternal glycaemia control by insulin administration normalized these effects.