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Effect of placental restriction and neonatal exendin-4 treatment on postnatal growth, adult body composition, and in vivo glucose metabolism in the sheep
journal contribution
posted on 2015-09-01, 00:00 authored by Hong Liu, Christopher G Schultz, Miles J De Blasio, Anita M Peura, Gary K Heinemann, Himawan Harryanto, Damien S Hunter, Amy L Wooldridge, Karen L Kind, Lynne C Giles, Rebecca A Simmons, Julie OwensJulie Owens, Kathryn L GatfordIntrauterine growth restriction (IUGR) increases the risk of adult type 2 diabetes (T2D) and obesity. Neonatal exendin-4 treatment can prevent diabetes in the IUGR rat, but whether this will be effective in a species where the pancreas is more mature at birth is unknown. Therefore, we evaluated the effects of neonatal exendin-4 administration after experimental restriction of placental and fetal growth on growth and adult metabolic outcomes in sheep. Body composition, glucose tolerance, and insulin secretion and sensitivity were assessed in singleton-born adult sheep from control (CON; n = 6 females and 4 males) and placentally restricted pregnancies (PR; n = 13 females and 7 males) and in sheep from PR pregnancies that were treated with exendin-4 as neonates (daily sc injections of 1 nmol/kg exendin-4; PR + exendin-4; n = 11 females and 7 males). Placental restriction reduced birth weight (by 29%) and impaired glucose tolerance in the adult but did not affect adult adiposity, insulin secretion, or insulin sensitivity. Neonatal exendin-4 suppressed growth during treatment, followed by delayed catchup growth and unchanged adult adiposity. Neonatal exendin-4 partially restored glucose tolerance in PR progeny but did not affect insulin secretion or sensitivity. Although the effects on glucose tolerance are promising, the lack of effects on adult body composition, insulin secretion, and insulin sensitivity suggest that the neonatal period may be too late to fully reprogram the metabolic consequences of IUGR in species that are more mature at birth than rodents.
History
Journal
American journal of physiology: endocrinology and metabolismVolume
309Issue
6Pagination
E589 - E600Publisher
American Physiological SocietyLocation
Bethesda, Md.Publisher DOI
eISSN
1522-1555Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2015 the American Physiological SocietyUsage metrics
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No categories selectedKeywords
body compositionexendin-4glucose toleranceinsulin actionintrauterine growth restrictionAdiposityAnimalsAnimals, NewbornBlood GlucoseDiabetes Mellitus, Type 2Disease Models, AnimalEndometriumExenatideFemaleFetal Growth RetardationHypoglycemic AgentsInsulinInsulin ResistanceInsulin SecretionPeptidesPregnancyRandom AllocationSheepVenomsScience & TechnologyLife Sciences & BiomedicineEndocrinology & MetabolismPhysiologyBETA-CELL FUNCTIONFOR-GESTATIONAL-AGEINSULIN-SECRETIONBIRTH-WEIGHTFETAL-GROWTHFEEDING-ACTIVITYSKELETAL-MUSCLEHUMAN PANCREASLIFE-STYLEOBESITY
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