Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb

Gatford, Kathryn L., Sulaiman, Siti A., Mohammad, Saidatul N. B., De Blasio, Miles J., Harland, M. Lyn, Simmons, Rebecca A. and Owens, Julie A. 2013, Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb, PLoS One, vol. 8, no. 2, pp. 1-10, doi: 10.1371/journal.pone.0056553.

Attached Files
Name Description MIMEType Size Downloads

Title Neonatal exendin-4 reduces growth, fat deposition and glucose tolerance during treatment in the intrauterine growth-restricted lamb
Author(s) Gatford, Kathryn L.
Sulaiman, Siti A.
Mohammad, Saidatul N. B.
De Blasio, Miles J.
Harland, M. Lyn
Simmons, Rebecca A.
Owens, Julie A.ORCID iD for Owens, Julie A.
Journal name PLoS One
Volume number 8
Issue number 2
Article ID e56553
Start page 1
End page 10
Total pages 10
Publisher Public Library of Science (PLoS)
Place of publication San Francisco, Calif.
Publication date 2013
ISSN 1932-6203
Keyword(s) Adipose Tissue
Animals, Newborn
Body Composition
Body Size
Cell Size
Fetal Development
Fetal Growth Retardation
Glucose Tolerance Test
Insulin Secretion
Insulin-Secreting Cells
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Summary 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 (1⁻¹, 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. PRINCIPAL 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.
Language eng
DOI 10.1371/journal.pone.0056553
Field of Research MD Multidisciplinary
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2013 Gatford et al.
Persistent URL

Document type: Journal Article
Collection: Office of the Deputy Vice-Chancellor (Research)
Connect to link resolver
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 14 times in TR Web of Science
Scopus Citation Count Cited 12 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 106 Abstract Views, 1 File Downloads  -  Detailed Statistics
Created: Wed, 16 Jan 2019, 14:26:14 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact