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Maternal Diabetes-Induced Hyperglycemia and Acute Intracerebral Hyperinsulinism Suppress Fetal Brain Neuropeptide Y Concentrations¹

Pediatric Research Institute (B.S.S.), Cardinal Glennon Children’s Hospital (B.S.S.), and the Departments of Pediatrics (B.S.S.) and Pharmacological and Physiological Sciences (T.C.W.), St. Louis University School of Medicine, St. Louis, Missouri 63110; and the Division of Neonatology and Developmental Biology, Department of Pediatrics, University of Pittsburgh, Magee-Womens Research Institute (S.U.D.), Pittsburgh, Pennsylvania 15213

Address all correspondence and requests for reprints to: Dr. Sherin U. Devaskar, Department of Pediatrics, 300 Halket Street, Pittsburgh, Pennsylvania 15213-3180.

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 nondiabetic (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 6-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 intracerebroventricular hyperinsulinism additively can inhibit various intrauterine and immediate postnatal NPY-mediated biological functions.

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