Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction

James S. Barry, Paul J. Rozance, Laura D. Brown, Russell V. Anthony, Kent Thornburg, William W. Hay

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    Unlike other visceral organs, myocardial weight is maintained in relation to fetal body weight in intrauterine growth restriction (IUGR) fetal sheep despite hypoinsulinemia and global nutrient restriction. We designed experiments in fetal sheep with placental insufficiency and restricted growth to determine basal and insulin-stimulated myocardial glucose and oxygen metabolism and test the hypothesis that myocardial insulin sensitivity would be increased in the IUGR heart. IUGR was induced by maternal hyperthermia during gestation. Control (C) and IUGR fetal myocardial metabolism were measured at baseline and under acute hyperinsulinemic/euglycemic clamp conditions at 128–132 days gestation using fluorescent microspheres to determine myocardial blood flow. Fetal body and heart weights were reduced by 33% (P = 0.008) and 30% (P = 0.027), respectively. Heart weight to body weight ratios were not different. Basal left ventricular (LV) myocardial blood flow per gram of LV tissue was maintained in IUGR fetuses compared to controls. Insulin increased LV myocardial blood flow by ∼38% (P <0.01), but insulin-stimulated LV myocardial blood flow in IUGR fetuses was 73% greater than controls. Similar to previous reports testing acute hypoxia, LV blood flow was inversely related to arterial oxygen concentration (r2= 0.71) in both control and IUGR animals. Basal LV myocardial glucose delivery and uptake rates were not different between IUGR and control fetuses. Insulin increased LV myocardial glucose delivery (by 40%) and uptake (by 78%) (P <0.01), but to a greater extent in the IUGR fetuses compared to controls. During basal and hyperinsulinemic–euglycemic clamp conditions LV myocardial oxygen delivery, oxygen uptake, and oxygen extraction efficiency were not different between groups. These novel results demonstrate that the fetal heart exposed to nutrient and oxygen deprivation from placental insufficiency appears to maintain myocardial energy supply in the IUGR condition via increased glucose uptake and metabolic response to insulin, which support myocardial function and growth.

    Original languageEnglish (US)
    Pages (from-to)839-847
    Number of pages9
    JournalExperimental Biology and Medicine
    Volume241
    Issue number8
    DOIs
    StatePublished - 2015

    Fingerprint

    Fetal Development
    Metabolism
    Insulin Resistance
    Sheep
    Insulin
    Glucose
    Growth
    Oxygen
    Blood
    Fetus
    Placental Insufficiency
    Fetal Heart
    Fetal Weight
    Clamping devices
    Nutrients
    Food
    Pregnancy
    Induced Hyperthermia
    Glucose Clamp Technique
    Organ Size

    Keywords

    • fetus
    • Glucose
    • heart
    • insulin
    • myocardial
    • sheep

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction. / Barry, James S.; Rozance, Paul J.; Brown, Laura D.; Anthony, Russell V.; Thornburg, Kent; Hay, William W.

    In: Experimental Biology and Medicine, Vol. 241, No. 8, 2015, p. 839-847.

    Research output: Contribution to journalArticle

    Barry, James S. ; Rozance, Paul J. ; Brown, Laura D. ; Anthony, Russell V. ; Thornburg, Kent ; Hay, William W. / Increased fetal myocardial sensitivity to insulin-stimulated glucose metabolism during ovine fetal growth restriction. In: Experimental Biology and Medicine. 2015 ; Vol. 241, No. 8. pp. 839-847.
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