The effects of maternal diabetes on expression of insulin-like growth factor-1 and insulin receptors in male developing rat hippocampus

Diabetes during pregnancy causes neurodevelopmental and neurocognitive abnormalities in offspring. Insulin and insulin-like growth factor-1 (IGF-1) are important regulators of developmental and cognitive functions in the central nervous system. We examined the effects of maternal diabetes on insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression in the developing rat hippocampus. Female rats were maintained diabetic from a week before pregnancy through parturition and male offspring was killed at P0, P7, and P14. We found a significant bilateral upregulation of both IGF-1R and InsR transcripts in the hippocampus of pups born to diabetic mothers at P0, as compared to controls. However, at the same time point, the results of western blot analysis revealed only a slight change in their protein levels. At P7, there was a marked bilateral reduction in mRNA expression and protein levels of IGF-1R, although not of InsR in the diabetic group. We also found a downregulation in IGF1-R transcripts, especially in left hippocampus of the diabetic group at P14. Moreover, at the same time point, InsR expression was significantly decreased in both hippocampi of diabetic newborns. When compared with controls, we did not find any difference in hippocampal IGF-1R or InsR mRNA and protein levels in the insulin-treated group. The present study revealed that diabetes during pregnancy strongly influences the regulation of both IGF-1R and InsR in the right/left developing hippocampi. Furthermore, the rigid control of maternal glycaemia by insulin administration normalized these effects.