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 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.
Singh
B S
BS
Pediatric Research Institute, Cardinal Glennon Children's Hospital, St. Louis University School of Medicine, Missouri 63110, USA.
Westfall
T C
TC
Devaskar
S U
SU
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D001927:Brain Diseases / Q000209:etiology / Q000378:metabolism; D005260:Female; D005315:Fetal Diseases / Q000209:etiology / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D006943:Hyperglycemia / Q000209:etiology; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009994:Osmolar Concentration; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009478:Neuropeptide Y