Maternal diabetes-induced hyperglycemia and acute intracerebral hyperinsulinism suppress fetal brain neuropeptide Y concentrations

We examined the effect of streptozotocin-induced maternal diabetes of 6-day duration and 4- to 24-h intracerebroventricular and systemic hyperinsulinism on fetal brain neuropeptide Y (NPY) synthesis and concentrations. Maternal diabetes (n=6) leading to fetal hyperglycemia (5-fold increase; P <0.05) and normoinsulinemia caused a 40% decline (P <0.05) in fetal brain NPY messenger RNA (mRNA) and a 50% decline (P <0.05) in NPY radioimmunoassayable levels compared to levels in streptozotocin-treated nondiabetis (n=7) and vehicle-treated control (n=8) animals. In contrast, systemic hyperinsulinemia (n=7) of 5- to 100-fold increase (P <0.05) over the respective control (n=7) with normoglycemia caused an insignificant (20-30%) decrease in fetal brain NPY mRNA and protein concentrations. However, fetal intracerebroventricular hyperinsulinism (n=7) with no change in fetal glucose concentrations caused a 50-60% decline (P <0.05) in only the NPY peptide levels, with no change in the corresponding mRNA amounts. We conclude that fetal hyperglycemia of B-day duration and intracerebroventricular hyperinsulinism of 4-24 h suppress fetal brain NPY concentrations, the former by a pretranslational and the latter by either a translational/posttranslational mechanism or depletion of intracellular secretory stores. We speculate that fetal hyperglycemia and intracerebroventrieular hy. perinsulinism additively can inhibit various intrauterine and immediate postnatal NPY-mediated biological functions.