Effect of placental restriction and neonatal exendin-4 treatment on postnatal growth, adult body composition, and in vivo glucose metabolism in the sheep

Effect of placental restriction and neonatal exendin-4 treatment on postnatal growth, adult body composition, and in vivo glucose metabolism in the sheep

Intrauterine 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...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism Vol. 309; no. 6; p. E589
Main Authors: Liu, Hong, Schultz, Christopher G, De Blasio, Miles J, Peura, Anita M, Heinemann, Gary K, Harryanto, Himawan, Hunter, Damien S, Wooldridge, Amy L, Kind, Karen L, Giles, Lynne C, Simmons, Rebecca A, Owens, Julie A, Gatford, Kathryn L
Format: Journal Article
Language:English
Published: United States 15-09-2015
Subjects:
Adiposity - drug effects
Animals
Animals, Newborn
Blood Glucose - drug effects
Blood Glucose - metabolism
Body Composition - drug effects
Diabetes Mellitus, Type 2 - metabolism
Diabetes Mellitus, Type 2 - prevention & control
Disease Models, Animal
Endometrium - surgery
Exenatide
Female
Fetal Growth Retardation - metabolism
Hypoglycemic Agents - pharmacology
Insulin - metabolism
Insulin Resistance
Insulin Secretion
Peptides - pharmacology
Pregnancy
Random Allocation
Sheep
Venoms - pharmacology
insulin action
intrauterine growth restriction
body composition
glucose tolerance
exendin-4
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Summary:Intrauterine 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.
ISSN:1522-1555
DOI:10.1152/ajpendo.00487.2014