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.

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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. orcid.org/0000-0002-7498-1353
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
Animals, Newborn
Body Composition
Body Size
Cell Size
Exenatide
Fetal Development
Fetal Growth Retardation
Glucose Tolerance Test
Humans
Insulin
Insulin Secretion
Insulin-Secreting Cells
Peptides
Sheep
Venoms
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
GLUCAGON-LIKE PEPTIDE-1
BETA-CELL FUNCTION
CARDIOVASCULAR RISK-FACTORS
MESSENGER-RNA EXPRESSION
GESTATION FETAL SHEEP
INSULIN SENSITIVITY
PLACENTAL RESTRICTION
BIRTH-WEIGHT
EXENATIDE EXENDIN-4
GLYCEMIC CONTROL
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 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. 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 http://hdl.handle.net/10536/DRO/DU:30116329

Document type: Journal Article
Collection: Office of the Deputy Vice-Chancellor Research
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