Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney

We have recently demonstrated that the exposure to hyperglycemia in utero i mpairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations in the IG F system in fetal tissues. It has also been shown that both IGF-I and IGF-I I are produced within developing metanephros and promote renal organogenesi s. Therefore, we investigated the effect of maternal diabetes on IGFs and t heir receptors in developing fetal rat kidney. Diabetes was induced in preg nant rats by a single injection of streptozotocin on day 0 of gestation. We measured the amounts of IGF and their receptors, both proteins and mRNAs, in the metanephroi of fetuses issued from diabetic subjects and in age-matc hed fetuses from control subjects (14-20 days of gestation). IGF-II was pro duced throughout fetal nephrogenesis, whereas IGF-I protein was not detecte d, suggesting a critical role of IGF-II in kidney development. Fetal exposu re to maternal diabetes caused no change in IGF production in the early sta ges of nephrogenesis. Similarly, the amounts of IGF-I receptor and insulin receptor were not altered. By contrast, there was an increase in production of IGF-II/mannose-6-phosphate receptor throughout nephrogenesis. Because t his receptor plays an essential role in regulating the action of IGF-II, th e altered nephrogenesis in fetuses exposed to maternal diabetes may be link ed to a decrease in IGF-II bioavailability.