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Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.
J Physiol. 2017 08 01; 595(15):5103-5113.JP

Abstract

Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants.

Authors+Show Affiliations

School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ, USA.Perinatal Research Center, University of Colorado School of Medicine, Aurora, CO, USA.

Pub Type(s)

Journal Article
Review
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28194805

Citation

Limesand, Sean W., and Paul J. Rozance. "Fetal Adaptations in Insulin Secretion Result From High Catecholamines During Placental Insufficiency." The Journal of Physiology, vol. 595, no. 15, 2017, pp. 5103-5113.
Limesand SW, Rozance PJ. Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency. J Physiol (Lond). 2017;595(15):5103-5113.
Limesand, S. W., & Rozance, P. J. (2017). Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency. The Journal of Physiology, 595(15), 5103-5113. https://doi.org/10.1113/JP273324
Limesand SW, Rozance PJ. Fetal Adaptations in Insulin Secretion Result From High Catecholamines During Placental Insufficiency. J Physiol (Lond). 2017 08 1;595(15):5103-5113. PubMed PMID: 28194805.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency. AU - Limesand,Sean W, AU - Rozance,Paul J, Y1 - 2017/05/26/ PY - 2016/11/29/received PY - 2017/02/06/accepted PY - 2017/2/15/pubmed PY - 2018/4/20/medline PY - 2017/2/15/entrez KW - developmental programming KW - epinephrine KW - intrauterine growth restriction KW - norepinephrine KW - β-cell SP - 5103 EP - 5113 JF - The Journal of physiology JO - J. Physiol. (Lond.) VL - 595 IS - 15 N2 - Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants. SN - 1469-7793 UR - https://www.unboundmedicine.com/medline/citation/28194805/Fetal_adaptations_in_insulin_secretion_result_from_high_catecholamines_during_placental_insufficiency_ L2 - https://doi.org/10.1113/JP273324 DB - PRIME DP - Unbound Medicine ER -