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Elevated plasma norepinephrine inhibits insulin secretion, but adrenergic blockade reveals enhanced β-cell responsiveness in an ovine model of placental insufficiency at 0.7 of gestation

Published online by Cambridge University Press:  10 April 2013

A. R. Macko ,
D. T. Yates ,
X. Chen ,
A. S. Green ,
A. C. Kelly ,
L. D. Brown  and
S. W. Limesand
A. R. Macko
Affiliation:
Department of Animal Sciences, The University of Arizona, Tucson, AZ, USA
D. T. Yates
Affiliation:
Department of Animal Sciences, The University of Arizona, Tucson, AZ, USA
X. Chen
Affiliation:
Department of Animal Sciences, The University of Arizona, Tucson, AZ, USA
A. S. Green
Affiliation:
Department of Animal Sciences, The University of Arizona, Tucson, AZ, USA
A. C. Kelly
Affiliation:
Department of Animal Sciences, The University of Arizona, Tucson, AZ, USA
L. D. Brown
Affiliation:
Department of Pediatrics, Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA
S. W. Limesand*
Affiliation:
Department of Animal Sciences, The University of Arizona, Tucson, AZ, USA
*
*Address for correspondence: S. W. Limesand, Department of Animal Sciences, University of Arizona, 1650 E Limberlost Dr., Tucson AZ 85719, USA. (Email limesand@ag.arizona.edu)
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Abstract

In pregnancies complicated by placental insufficiency (PI), fetal hypoglycemia and hypoxemia progressively worsen during the third trimester, which increases circulating norepinephrine (NE). Pharmacological adrenergic blockade (ADR-block) at 0.9 gestation revealed that NE inhibits insulin secretion and enhanced β-cell responsiveness in fetuses with PI-induced intrauterine growth restriction (IUGR). NE concentrations in PI fetuses at 0.7 gestation were threefold greater compared with age-matched controls, but the levels were similar to near-term controls. Therefore, our objective was to determine whether elevations in plasma NE concentrations inhibit insulin secretion and produce compensatory β-cell responsiveness in PI fetuses at 0.7 gestation. Fetal insulin was measured under basal, glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-stimulated insulin secretion (GPAIS) conditions in the absence and presence of an ADR-block. Placental weights were 38% lower (P < 0.05) in PI fetus than in controls, but fetal weights were not different. PI fetuses had lower (P < 0.05) basal blood oxygen content, plasma glucose, insulin-like growth factor-1 and insulin concentrations and greater plasma NE concentrations (891 ± 211 v. 292 ± 65 pg/ml; P < 0.05) than controls. GSIS was lower in PI fetuses than in controls (0.34 ± 0.03 v. 1.08 ± 0.06 ng/ml; P < 0.05). ADR-block increased GSIS in PI fetuses (1.19 ± 0.11 ng/ml; P < 0.05) but decreased GSIS in controls (0.86 ± 0.02 ng/ml; P < 0.05). Similarly, GPAIS was 44% lower (P < 0.05) in PI fetuses than in controls, and ADR-block increased (P < 0.05) GPAIS in PI fetuses but not in controls. Insulin content per islet was not different between treatments. We conclude that elevations in fetal plasma NE suppress insulin concentrations, and that compensatory β-cell stimulus-secretion responsiveness is present before IUGR.

Keywords

adrenergic receptorsfetusintrauterine growth restrictionpancreas
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 4 , Issue 5 , October 2013 , pp. 402 - 410
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2013 

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