The transition from fetal growth restriction to accelerated postnatal growth: A potential role for insulin signalling in skeletal muscle

B. S. Muhlhausler, J. A. Duffield, S. E. Ozanne, C. Pilgrim, N. Turner, J. L. Morrison, I. Caroline McMillen

    Research output: Contribution to journalArticle

    71 Citations (Scopus)

    Abstract

    A world-wide series of epidemiological and experimental studies have demonstrated that there is an association between being small at birth, accelerated growth in early postnatal life and the emergence of insulin resistance in adult life. The aim of this study was to investigate why accelerated growth occurs in postnatal life after in utero growth restriction. Samples of quadriceps muscle were collected at ∼140 days gestation (term ∼150 days gestation) from normally grown fetal lambs (Control, n = 7) and from growth restricted fetal lambs (placentally restricted: PR, n = 8) and from Control (n = 14) and PR (n = 9) lambs at 21 days after birth. The abundance of the insulin and IGF1 receptor protein was higher in the quadriceps muscle of the PR fetus, but there was a lower abundance of the insulin signalling molecule PKCζ, and GLUT4 protein in the PR group. At 21 days of postnatal age, insulin receptor abundance remained higher in the muscle of the PR lamb, and there was also an up-regulation of the insulin signalling molecules, PI3Kinase p85, Akt1 and Akt2 and of the GLUT4 protein in the PR group. Fetal growth restriction therefore results in an increased abundance of the insulin receptor in skeletal muscle, which persists after birth when it is associated with an upregulation of insulin signalling molecules and the glucose transporter, GLUT4. These data provide evidence that the origins of the accelerated growth experienced by the small baby after birth lie in the adaptive response of the growth restricted fetus to its low placental substrate supply.

    LanguageEnglish
    Pages4199-4211
    Number of pages13
    JournalJournal of Physiology
    Volume587
    Issue number17
    DOIs
    Publication statusPublished - 11 Sep 2009

    ASJC Scopus subject areas

    • Physiology

    Cite this

    Muhlhausler, B. S. ; Duffield, J. A. ; Ozanne, S. E. ; Pilgrim, C. ; Turner, N. ; Morrison, J. L. ; McMillen, I. Caroline. / The transition from fetal growth restriction to accelerated postnatal growth : A potential role for insulin signalling in skeletal muscle. In: Journal of Physiology. 2009 ; Vol. 587, No. 17. pp. 4199-4211.
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    abstract = "A world-wide series of epidemiological and experimental studies have demonstrated that there is an association between being small at birth, accelerated growth in early postnatal life and the emergence of insulin resistance in adult life. The aim of this study was to investigate why accelerated growth occurs in postnatal life after in utero growth restriction. Samples of quadriceps muscle were collected at ∼140 days gestation (term ∼150 days gestation) from normally grown fetal lambs (Control, n = 7) and from growth restricted fetal lambs (placentally restricted: PR, n = 8) and from Control (n = 14) and PR (n = 9) lambs at 21 days after birth. The abundance of the insulin and IGF1 receptor protein was higher in the quadriceps muscle of the PR fetus, but there was a lower abundance of the insulin signalling molecule PKCζ, and GLUT4 protein in the PR group. At 21 days of postnatal age, insulin receptor abundance remained higher in the muscle of the PR lamb, and there was also an up-regulation of the insulin signalling molecules, PI3Kinase p85, Akt1 and Akt2 and of the GLUT4 protein in the PR group. Fetal growth restriction therefore results in an increased abundance of the insulin receptor in skeletal muscle, which persists after birth when it is associated with an upregulation of insulin signalling molecules and the glucose transporter, GLUT4. These data provide evidence that the origins of the accelerated growth experienced by the small baby after birth lie in the adaptive response of the growth restricted fetus to its low placental substrate supply.",
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    The transition from fetal growth restriction to accelerated postnatal growth : A potential role for insulin signalling in skeletal muscle. / Muhlhausler, B. S.; Duffield, J. A.; Ozanne, S. E.; Pilgrim, C.; Turner, N.; Morrison, J. L.; McMillen, I. Caroline.

    In: Journal of Physiology, Vol. 587, No. 17, 11.09.2009, p. 4199-4211.

    Research output: Contribution to journalArticle

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    T2 - Journal of Physiology

    AU - Muhlhausler, B. S.

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    AU - Ozanne, S. E.

    AU - Pilgrim, C.

    AU - Turner, N.

    AU - Morrison, J. L.

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