Hepatic glucose regulation and metabolism in adult sheep : effects of prenatal betamethasone

Deborah Sloboda, T.J.M. Moss, Shaofu Li, Dorota Doherty, Ilias Nitsos, J.R.G. Challis, John Newnham

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)

    Abstract

    Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hepatic 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) and corticosteroid-binding globulin (CBG) protein levels and insulin resistance in postnatal life. The aim was to determine whether these changes persisted to adulthood and whether alterations in mediators of hepatic glucocorticoid and glucose regulation contributed to changes in metabolism. Pregnant ewes or their fetuses received either repeated intramuscular saline (MS, FS) or betamethasone injections (0.5 mg/kg; M4, F4) at 104, 111, 118, and 124 days of gestation (dG), or a single betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG (M1, F1). Offspring were catheterized at 2 and 3 yr of age and given an intravenous glucose challenge ( 0.5 mg/kg). Hepatic tissue was collected at 3.5 yr. At 2 yr of age, basal plasma insulin was elevated in M4 offspring and at 3 yr of age was elevated in F4 offspring. Basal insulin-to-glucose ratio was significantly elevated in M4 offspring at 2 yr of age and elevated in M1, M4, and F4 offspring at 3 yr of age. All betamethasone treatments resulted in significant increases in hepatic glucose-6-phosphatase (G-6-Pase) activity. Hepatic glucocorticoid receptor protein levels were not altered in M1 and M4 offspring but were increased in F1 and F4 offspring. Hepatic CBG protein levels were lower in F4 but not F1 offspring and were unchanged from control in M1 and M4 offspring. Prenatal betamethasone exposure results in elevated hepatic G-6-Pase activity in adulthood and may contribute to long-term changes in metabolism.
    Original languageEnglish
    Pages (from-to)721-728
    JournalAmerican journal of physiology : endocrinology and metabolism
    Volume289
    Issue number4
    DOIs
    Publication statusPublished - 2005

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