Impaired ß-cell function and inadequate compensatory increases in ß-cell mass after intrauterine growth restriction in sheep

Gatford, Kathryn L., Mohammad, Saidatul N. B., Harland, M. Lyn, De Blasio, Miles J., Fowden, Abigail L., Robinson, Jeffrey S. and Owens, Julie A. 2008, Impaired ß-cell function and inadequate compensatory increases in ß-cell mass after intrauterine growth restriction in sheep, Endocrinology, vol. 149, no. 10, pp. 5118-5127, doi: 10.1210/en.2008-0233.

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Title Impaired ß-cell function and inadequate compensatory increases in ß-cell mass after intrauterine growth restriction in sheep
Author(s) Gatford, Kathryn L.
Mohammad, Saidatul N. B.
Harland, M. Lyn
De Blasio, Miles J.
Fowden, Abigail L.
Robinson, Jeffrey S.
Owens, Julie A.ORCID iD for Owens, Julie A.
Journal name Endocrinology
Volume number 149
Issue number 10
Start page 5118
End page 5127
Total pages 10
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2008-10
ISSN 0013-7227
Keyword(s) Adaptation, Physiological
Birth Weight
Calcium Channels, L-Type
Cell Count
Fetal Growth Retardation
Fetal Weight
Gene Expression
Gestational Age
Insulin Secretion
Insulin-Like Growth Factor I
Insulin-Like Growth Factor II
Insulin-Secreting Cells
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Summary Poor growth before birth increases the risk of non-insulin-dependent diabetes mellitus (NIDDM) and impairs insulin secretion relative to sensitivity. We investigated the effects of intrauterine growth restriction in sheep on insulin secretion, beta-cell mass, and function from before birth to young adulthood and its molecular basis. Pancreas was collected from control and placentally restricted sheep as fetuses (d 143 gestation), lambs (aged 42 d), and young adults (aged 556 d), following independent measures of in vivo insulin secretion and sensitivity. beta-Cells and islets were counted after immunohistochemical staining for insulin. In lambs, gene expression was measured by RT-PCR and expressed relative to 18S. beta-Cell mass correlated positively with fetal weight but negatively with birth weight in adult males. Glucose-stimulated insulin disposition and beta-cell function correlated negatively with fetal weight but positively with birth weight in adult males. Placental restriction increased pancreatic expression of IGF-II and IGF-I but decreased that of voltage-gated calcium channel, alpha1D subunit (CACNA1D) in lambs. In male lambs, pancreatic IGF-II and insulin receptor expression correlated strongly and positively with beta-cell mass and CACNA1D expression with glucose-stimulated insulin disposition. Restricted growth before birth in the sheep does not impair insulin secretion, relative to sensitivity, before birth or in young offspring. IGF-II and insulin receptor are implicated as key molecular regulators of beta-cell mass compensation, whereas impaired expression of the voltage-gated calcium channel may underlie impaired beta-cell function after intrauterine growth restriction. With aging, the insulin secretory capacity of the beta-cell is impaired in males, and their increases in beta-cell mass are inadequate to maintain adequate insulin secretion relative to sensitivity.
Language eng
DOI 10.1210/en.2008-0233
Field of Research 07 Agricultural And Veterinary Sciences
11 Medical And Health Sciences
06 Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, The Endocrine Society
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Document type: Journal Article
Collection: Office of the Deputy Vice-Chancellor (Research)
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