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Cross-fostering and improved lactation ameliorates deficits in endocrine pancreatic morphology in growth-restricted adult male rat offspring

Published online by Cambridge University Press:  19 July 2010

A. L. Siebel ,
L. A. Gallo ,
T. C. Guan ,
J. A. Owens  and
M. E. Wlodek
A. L. Siebel
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
L. A. Gallo
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
T. C. Guan
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
J. A. Owens
Affiliation:
School of Pediatrics and Reproductive Health, Disciplines of Obstetrics and Gynecology, University of Adelaide, Adelaide, South Australia, Australia
M. E. Wlodek*
Affiliation:
Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
*
Address for correspondence: M. E. Wlodek, Department of Physiology, The University of Melbourne, VIC 3010, Australia. (Email [email protected])
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Abstract

Uteroplacental insufficiency and poor postnatal nutrition impair adult glucose tolerance and insulin secretion in male rat offspring, which can be partially ameliorated by improving postnatal nutrition. Uteroplacental insufficiency was induced in the WKY rat on day 18 of pregnancy (Restricted) compared to sham-operated Controls. Pups were then cross-fostered onto Control or Restricted mothers one day after birth resulting in: (Pup-on-Mother) Control-on-Control, Control-on-Restricted, Restricted-on-Control and Restricted-on-Restricted. Endocrine pancreatic morphology and markers of intrinsic β-cell function and glucose homeostasis were assessed in male offspring at 6 months. Pancreatic and hepatic gene expression was quantified at postnatal day 7 and 6 months. Restricted pups were born 10–15% lighter than Controls and remained lighter at 6 months. Relative islet and β-cell mass were 51–65% lower in Restricted-on-Restricted compared to Controls at 6 months. Non-fasting plasma C-reactive protein levels were also increased, suggestive of an inflammatory response. Overall, the average number of islets, small islets and proportion of β-cells per islet correlated positively with birth weight. Intrinsic β-cell function, estimated by insulin secretion relative to β-cell mass, was unaffected by Restriction, suggesting that the in vivo functional deficit was attributable to reduced mass, not function. Importantly, these deficits were ameliorated when lactational nutrition was normalized in Restricted-on-Control offspring, who also showed increased pancreatic Igf1r, Pdx1 and Vegf mRNA expression at 7 days compared to Control-on-Control and Restricted-on-Restricted. This highlights lactation as a critical period for intervention following prenatal restraint, whereby deficits in endocrine pancreatic mass and associated impaired in vivo insulin secretion can be ameliorated.

Keywords

gene expressionnutritionpancreatic β-cell
Type
Original Articles
Information
Journal of Developmental Origins of Health and Disease , Volume 1 , Issue 4 , August 2010 , pp. 234 - 244
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2010

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