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Type: Journal article
Title: Cross-fostering and improved lactation ameliorates deficits in endocrine pancreatic morphology in growth-restricted adult male rat offspring
Author: Siebel, A.
Gallo, J.
Guan, T.
Owens, J.
Wlodek, M.
Citation: Journal of Developmental Origins of Health and Disease, 2010; 1(4):234-244
Publisher: Cambridge University Press
Issue Date: 2010
ISSN: 2040-1744
Statement of
A. L. Siebel, L. A. Gallo, T. C. Guan, J. A. Owens and M. E. Wlodek
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 expression
pancreatic β-cell
Rights: Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2010
DOI: 10.1017/S2040174410000383
Appears in Collections:Aurora harvest 5
Obstetrics and Gynaecology publications

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