Elevated Fetal Plasma Norepinephrine Elicits Perinatal Adaptations in β-Cell Function

Persistent Link:
http://hdl.handle.net/10150/311460
Title:
Elevated Fetal Plasma Norepinephrine Elicits Perinatal Adaptations in β-Cell Function
Author:
Macko, Antoni Ryszard
Issue Date:
2013
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The objective of this dissertation research was to determine the specific actions of chronically elevated catecholamines on; 1.) fetal growth and ß-cell function during the third trimester in vivo in an ovine model of placental insufficiency-induced intrauterine growth restriction (PI-IUGR), and 2.) regulation of insulin secretion in vitro utilizing the mouse insulinoma cell line Min6.At 0.7-gestation, fetal weights were not different but PI fetuses had lower (P<0.05) basal blood oxygen content, plasma glucose, IGF-1, and insulin concentrations and greater norepinephrine concentrations (891±211 vs. 292±65 pg/ml; P<0.05) compared to controls. Glucose-stimulated insulin secretion (GSIS) was lower in PI than control fetuses (0.34±0.03 vs. 1.08±0.06 ng/ml; P<0.05). ADR-block increased GSIS in PI fetuses (1.19±0.11) but decreased GSIS in controls (0.86±0.02 ng/ml). Insulin content per islet was not different between PI and control fetuses. We concluded that elevated fetal plasma norepinephrine, in PI fetuses at 0.7 gestation, precedes growth restriction and suppresses insulin concentrations, and ADR-block revealed compensatory β-cells stimulus-secretion responsiveness. Therefore, to determine the effects of chronic hypercatecholamine exposure on fetal growth and β-cell function independent of hypoglycemia and hypoxemia, we performed surgical sham or adrenal demedullation (AD) at 0.65 gestation on control and IUGR fetuses (n= 5 Control-Sham, 5 Control-AD, 5 IUGR-Sham, 5 IUGR-AD fetuses). Studies commenced at 0.9 gestation under ambient conditions and steady-state reversal of arterial pO2 between IUGR and control fetuses. Plasma norepinephrine was 5-fold higher in IUGR-Sham vs. Control-Sham and reduced in IUGR-AD fetuses to concentrations not different from Control-Sham fetuses. Fetal mass was lower in IUGR vs. control fetuses but 92% greater in IUGR-AD compared to IUGR-Sham fetuses. Basal plasma glucose and arterial pO2 were lower in IUGR-Sham vs. Control-Sham, and IUGR-AD vs. Control-AD fetuses. Basal and glucose-stimulated insulin concentrations compared to Control-Sham were lower in IUGR-Sham and IUGR-AD and Control-AD fetuses. Oxygenation improved GSIS in IUGR-Sham and IUGR-AD fetuses. In conclusion, hypoglycemia, hypoxemia and norepinephrine interdependently and differentially regulate aspects of fetal growth and β-cell function in the IUGR fetus. In Min6 cells, we determined that GSIS responsiveness is enhanced and adrenergic receptor α2A is desensitized cells following chronic exposure to epinephrine.
Type:
text; Electronic Dissertation
Keywords:
Fetal; Metabolism; Norepinephrine; β-Cell; Physiological Sciences; Endocrinology
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Physiological Sciences
Degree Grantor:
University of Arizona
Advisor:
Limesand, Sean W.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleElevated Fetal Plasma Norepinephrine Elicits Perinatal Adaptations in β-Cell Functionen_US
dc.creatorMacko, Antoni Ryszarden_US
dc.contributor.authorMacko, Antoni Ryszarden_US
dc.date.issued2013-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe objective of this dissertation research was to determine the specific actions of chronically elevated catecholamines on; 1.) fetal growth and ß-cell function during the third trimester in vivo in an ovine model of placental insufficiency-induced intrauterine growth restriction (PI-IUGR), and 2.) regulation of insulin secretion in vitro utilizing the mouse insulinoma cell line Min6.At 0.7-gestation, fetal weights were not different but PI fetuses had lower (P<0.05) basal blood oxygen content, plasma glucose, IGF-1, and insulin concentrations and greater norepinephrine concentrations (891±211 vs. 292±65 pg/ml; P<0.05) compared to controls. Glucose-stimulated insulin secretion (GSIS) was lower in PI than control fetuses (0.34±0.03 vs. 1.08±0.06 ng/ml; P<0.05). ADR-block increased GSIS in PI fetuses (1.19±0.11) but decreased GSIS in controls (0.86±0.02 ng/ml). Insulin content per islet was not different between PI and control fetuses. We concluded that elevated fetal plasma norepinephrine, in PI fetuses at 0.7 gestation, precedes growth restriction and suppresses insulin concentrations, and ADR-block revealed compensatory β-cells stimulus-secretion responsiveness. Therefore, to determine the effects of chronic hypercatecholamine exposure on fetal growth and β-cell function independent of hypoglycemia and hypoxemia, we performed surgical sham or adrenal demedullation (AD) at 0.65 gestation on control and IUGR fetuses (n= 5 Control-Sham, 5 Control-AD, 5 IUGR-Sham, 5 IUGR-AD fetuses). Studies commenced at 0.9 gestation under ambient conditions and steady-state reversal of arterial pO2 between IUGR and control fetuses. Plasma norepinephrine was 5-fold higher in IUGR-Sham vs. Control-Sham and reduced in IUGR-AD fetuses to concentrations not different from Control-Sham fetuses. Fetal mass was lower in IUGR vs. control fetuses but 92% greater in IUGR-AD compared to IUGR-Sham fetuses. Basal plasma glucose and arterial pO2 were lower in IUGR-Sham vs. Control-Sham, and IUGR-AD vs. Control-AD fetuses. Basal and glucose-stimulated insulin concentrations compared to Control-Sham were lower in IUGR-Sham and IUGR-AD and Control-AD fetuses. Oxygenation improved GSIS in IUGR-Sham and IUGR-AD fetuses. In conclusion, hypoglycemia, hypoxemia and norepinephrine interdependently and differentially regulate aspects of fetal growth and β-cell function in the IUGR fetus. In Min6 cells, we determined that GSIS responsiveness is enhanced and adrenergic receptor α2A is desensitized cells following chronic exposure to epinephrine.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectFetalen_US
dc.subjectMetabolismen_US
dc.subjectNorepinephrineen_US
dc.subjectβ-Cellen_US
dc.subjectPhysiological Sciencesen_US
dc.subjectEndocrinologyen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorLimesand, Sean W.en_US
dc.contributor.committeememberLimesand, Sean W.en_US
dc.contributor.committeememberCollier, Robert J.en_US
dc.contributor.committeememberHenriksen, Erik J.en_US
dc.contributor.committeememberLynch, Ronald M.en_US
dc.contributor.committeememberRenquist, Benjamin J.en_US
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