title: Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle.
abstract: We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 μg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure the protein content and gene expression of insulin receptor β (IRβ; INSR), IRβ Tyr 1361 phosphorylation (pIRβ), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKT and AKT1 (respectively, 73 and 72% from 0.67 GA control, P<0.001); IRβ and pIRβ were also decreased (respectively, 94 and 85%, P<0.01) in the muscle of premature GC-exposed fetuses but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P<0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation.
authors.affiliation: Neonatology Division, Department of Pediatrics Diabetes Division, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78229, USA Geriatric Research, Education, and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, 78229, USA Barshop Institute for Longevity and Aging Studies, 15355 Lambda Drive, San Antonio, Texas 78245, USA Department of Obstetrics, Center for Pregnancy and Newborn Research, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Blanco
authors.forename: Alvaro G
authors.initials: AG
authors.lastname: Moreira
authors.forename: Lisa L
authors.initials: LL
authors.lastname: McGill-Vargas
authors.forename: Diana G
authors.initials: DG
authors.lastname: Anzueto
authors.forename: Peter
authors.initials: P
authors.lastname: Nathanielsz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D000818:Animals; D000831:Animals, Newborn; D001724:Birth Weight / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D048529:Papio hamadryas; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D007328:Insulin
keywords: corticosteroid; fetus; glucocorticoid; insulin; muscle; preterm; primate
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