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. 2009 Sep 1;587(Pt 17):4199-211.
doi: 10.1113/jphysiol.2009.173161. Epub 2009 Jul 21.

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

B S Muhlhausler  1 , J A Duffield, S E Ozanne, C Pilgrim, N Turner, J L Morrison, I C McMillen
Affiliations

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

B S Muhlhausler et al. J Physiol. .

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 approximately 140 days gestation (term approximately 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 PKC, 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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Figures

Figure 1
Figure 1. The abundance of protein for the insulin receptor (IR, A and C) and IGF1 receptor (IGF1R, B and D) in quadriceps muscle in the Control (open bars) and PR (filled bars) fetus (A and B) and 21 d lamb (C and D)
Protein abundance is expressed as a percentage of the mean value of the Control group. *Significant effect of PR on protein abundance (P < 0.05).
Figure 3
Figure 3. The abundance of protein for Akt1 (A and D), Akt2 (B and E) and pAkt (C and F) in quadriceps muscle in the Control (open bars) and PR (filled bars) fetus (A, B and C) and 21 d lamb (D, E and F)
Protein abundance is expressed as a percentage of the mean value of the Control group. *Significant effect of PR on protein abundance (P < 0.05).
Figure 2
Figure 2. The abundance of protein for PI3K (A and C) and PKCζ (B and D) in quadriceps muscle in the Control (open bars) and PR (filled bars) fetus (A and B) and 21 d lamb (C and D)
Protein abundance is expressed as a percentage of the mean value of the Control group. *Significant effect of PR on protein abundance (P < 0.05).
Figure 4
Figure 4. The relative expression of GLUT4 mRNA (A and D), abundance of GLUT4 protein (B and E) and expression of GLUT1 mRNA (C and F) in quadriceps muscle in the Control (open bars) and PR (filled bars) fetus (A, B and C) and 21 d lamb (D, E and F)
The expression of GLUT1 and GLUT4 mRNA was normalised to the housekeeper gene ARP-P0. Protein abundance is expressed as a percentage of the mean value of the Control group. *Significant effect of PR on normalised mRNA expression or protein abundance (P < 0.05).
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