Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/78406
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Type: Journal article
Title: Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb
Author: Gatford, K.
Sulaiman, S.
Mohammad, S.
De Blasio, M.
Harland, M.
Simmons, R.
Owens, J.
Citation: PLoS One, 2013; 8(2):1-10
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
1932-6203
Statement of
Responsibility: 
Kathryn L. Gatford, Siti A. Sulaiman, Saidatul N. B. Mohammad, Miles J. De Blasio, M. Lyn Harland, Rebecca A. Simmons, Julie A. Owens
Abstract: BACKGROUND IUGR increases the risk of type 2 diabetes mellitus (T2DM) in later life, due to reduced insulin sensitivity and impaired adaptation of insulin secretion. In IUGR rats, development of T2DM can be prevented by neonatal administration of the GLP-1 analogue exendin-4. We therefore investigated effects of neonatal exendin-4 administration on insulin action and β-cell mass and function in the IUGR neonate in the sheep, a species with a more developed pancreas at birth. METHODS Twin IUGR lambs were injected s.c. daily with vehicle (IUGR+Veh, n = 8) or exendin-4 (1 nmol.kg-1, IUGR+Ex-4, n = 8), and singleton control lambs were injected with vehicle (CON, n = 7), from d 1 to 16 of age. Glucose-stimulated insulin secretion and insulin sensitivity were measured in vivo during treatment (d 12–14). Body composition, β-cell mass and in vitro insulin secretion of isolated pancreatic islets were measured at d 16. PRINCIPLE FINDINGS IUGR+Veh did not alter in vivo insulin secretion or insulin sensitivity or β-cell mass, but increased glucose-stimulated insulin secretion in vitro. Exendin-4 treatment of the IUGR lamb impaired glucose tolerance in vivo, reflecting reduced insulin sensitivity, and normalised glucose-stimulated insulin secretion in vitro. Exendin-4 also reduced neonatal growth and visceral fat accumulation in IUGR lambs, known risk factors for later T2DM. CONCLUSIONS Neonatal exendin-4 induces changes in IUGR lambs that might improve later insulin action. Whether these effects of exendin-4 lead to improved insulin action in adult life after IUGR in the sheep, as in the PR rat, requires further investigation.
Keywords: Adipose Tissue
Venoms
Animals
Animals, Newborn
Sheep
Humans
Fetal Growth Retardation
Insulin
Peptides
Glucose Tolerance Test
Body Size
Cell Size
Body Composition
Fetal Development
Insulin-Secreting Cells
Exenatide
Insulin Secretion
Rights: © 2013 Gatford et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.pone.0056553
Appears in Collections:Aurora harvest 4
Obstetrics and Gynaecology publications

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