The transition from fetal growth restriction to accelerated postnatal growth: a potential role for insulin signalling in skeletal muscle
- 27 August 2009
- journal article
- Published by Wiley in Journal Of Physiology-London
- Vol. 587 (17), 4199-4211
- https://doi.org/10.1113/jphysiol.2009.173161
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.This publication has 50 references indexed in Scilit:
- Altered PI3-Kinase/Akt Signalling in Skeletal Muscle of Young Men with Low Birth WeightPLOS ONE, 2008
- Intracellular Mechanisms of Metabolism Regulation: The Role of Signaling via the Mammalian Target of Rapamycin Pathway and Other RoutesThe American Journal of Cardiology, 2008
- Role of leptin in the regulation of growth and carbohydrate metabolism in the ovine fetus during late gestationJournal Of Physiology-London, 2008
- Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult ratAmerican Journal of Physiology-Endocrinology and Metabolism, 2008
- Restriction of placental growth in sheep impairs insulin secretion but not sensitivity before birthJournal Of Physiology-London, 2007
- The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complexThe Journal of cell biology, 2005
- Early growth restriction leads to down regulation of protein kinase C zeta and insulin resistance in skeletal muscleJournal of Endocrinology, 2003
- Size at birth, childhood growth and obesity in adult lifeInternational Journal of Obesity, 2001
- D-glucose transport and glycolytic enzyme activities in erythrocytes of dogs, pigs, cats, horses, cattle and sheepResearch in Veterinary Science, 1995
- Metabolic and endocrine findings in appropriate and small for gestational age fetusesjpme, 1991