Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle

Cynthia Blanco, Alvaro G Moreira, Lisa L. McGill-Vargas, Diana G. Anzueto, Peter Nathanielsz, Nicolas Musi

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 mg/kg) before delivery, while the other half received no intervention.Vastus lateralis muscle was obtained from postnatal animals tomeasure the protein content andgene expressionof 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 AKTand 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 themuscle of premature GC-exposed fetuses but not intermfetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (PZ0.09), 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.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalJournal of Endocrinology
Volume221
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Papio
Glucocorticoids
Adrenal Cortex Hormones
Skeletal Muscle
Insulin
Gestational Age
Fetus
Phosphorylation
Betamethasone
Pregnancy
Muscles
Proto-Oncogene Proteins c-akt
Facilitative Glucose Transport Proteins
Insulin Receptor
Quadriceps Muscle
Phosphatidylinositol 3-Kinases
Tyrosine
Signal Transduction
Proteins

Keywords

  • Corticosteroid
  • Fetus
  • Glucocorticoid
  • Insulin
  • Muscle
  • Preterm
  • Primate

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle. / Blanco, Cynthia; Moreira, Alvaro G; McGill-Vargas, Lisa L.; Anzueto, Diana G.; Nathanielsz, Peter; Musi, Nicolas.

In: Journal of Endocrinology, Vol. 221, No. 2, 2014, p. 253-260.

Research output: Contribution to journalArticle

Blanco, Cynthia ; Moreira, Alvaro G ; McGill-Vargas, Lisa L. ; Anzueto, Diana G. ; Nathanielsz, Peter ; Musi, Nicolas. / Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle. In: Journal of Endocrinology. 2014 ; Vol. 221, No. 2. pp. 253-260.
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