title: Chronically Increased Amino Acids Improve Insulin Secretion, Pancreatic Vascularity, and Islet Size in Growth-Restricted Fetal Sheep.
abstract: Placental insufficiency is associated with reduced supply of amino acids to the fetus and leads to intrauterine growth restriction (IUGR). IUGR fetuses are characterized by lower glucose-stimulated insulin secretion, smaller pancreatic islets with less β-cells, and impaired pancreatic vascularity. To test whether supplemental amino acids infused into the IUGR fetus could improve these complications of IUGR we used acute (hours) and chronic (11 d) direct fetal amino acid infusions into a sheep model of placental insufficiency and IUGR near the end of gestation. IUGR fetuses had attenuated acute amino acid-stimulated insulin secretion compared with control fetuses. These results were confirmed in isolated IUGR pancreatic islets. After the chronic fetal amino acid infusion, fetal glucose-stimulated insulin secretion and islet size were restored to control values. These changes were associated with normalization of fetal pancreatic vascularity and higher fetal pancreatic vascular endothelial growth factor A protein concentrations. These results demonstrate that decreased fetal amino acid supply contributes to the pathogenesis of pancreatic islet defects in IUGR. Moreover, the results show that pancreatic islets in IUGR fetuses retain their ability to respond to increased amino acids near the end of gestation after chronic fetal growth restriction.
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: Laura D
authors: LD
authors: Brown
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: Melissa
authors: M
authors: Davis
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: Sandra
authors: S
authors: Wai
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: Stephanie R
authors: SR
authors: Wesolowski
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: William W
authors: WW
authors: Hay
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: Sean W
authors: SW
authors: Limesand
authors: Perinatal Research Center (L.D.B., S.W., W.W.H., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045; School of Animal and Comparative Biomedical Sciences (M.D., S.W.L.), University of Arizona, Tucson, Arizona 85719; and Center for Women's Health Research (L.D.B., S.R.W., P.J.R.), University of Colorado School of Medicine, Aurora, Colorado 80045.
authors: Paul J
authors: PJ
authors: Rozance
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000628:therapy*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000098:blood supply / Q000187:drug effects*; D010927:Placental Insufficiency; D011247:Pregnancy; D012756:Sheep
chemical_list: D000596:Amino Acids; D007328:Insulin