HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 584/3/935    most recent jphysiol.2007.142141v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Owens, J. A. Articles by Fowden, A. L. Search for Related Content PubMed PubMed Citation Articles by Owens, J. A. Articles by Fowden, A. L. Related Collections Renal and Endocrine

¹ Department of Physiology, University of Adelaide, SA 5005, Australia
² Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK

Restricted growth before birth is associated with impaired insulin secretion but with initially enhanced insulin sensitivity in early postnatal life, which then progresses to insulin resistance and impaired glucose homeostasis by adulthood. This suggests that prenatal restraint impairs insulin secretion, but increases insulin sensitivity, before birth. Poor placental growth and function are major causes of restricted fetal growth in humans. We have therefore investigated the effects of restricted placental growth and function on plasma glucose, -amino nitrogen and insulin concentrations and glucose- and arginine-stimulated insulin secretion in the fetal sheep at 120 and 140 days gestational age, and on insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp, at 130 days gestational age. Placental restriction decreased fetal blood pH and oxygen content, and weight in late gestation by 20%. Reduced fetal and placental weights and indices of poor placental function, in particular fetal hypoxia and hypoglycaemia, were associated with impaired glucose- and arginine-stimulated insulin secretion, but not with changes in insulin sensitivity in the fetal sheep. We conclude that the impaired insulin secretion capacity reported in children and adults after intrauterine growth restriction, and in the neonatal and young adult sheep which is small at birth, is present in utero and persists. Whether this reflects the actions of the adverse intrauterine environment or changes to intrinsic capacity is unclear, but in utero interventions may be necessary to improve postnatal insulin secretion in the infant who is growth-restricted before birth.

(Received 1 August 2007; accepted after revision 28 August 2007; first published online 30 August 2007)
Corresponding author J. A. Owens: School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia. Email: julie.owens{at}adelaide.edu.au

This article has been cited by other articles:

				J. S. Gilbert, E. Brandon, and T. Vera Fetal insulin secretion in late gestation: does size matter? J. Physiol., December 15, 2007; 585(3): 651 - 652. [Full Text] [PDF]