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dc.contributor.authorChen, Xiaochuan
dc.contributor.authorKelly, Amy C
dc.contributor.authorYates, Dustin T
dc.contributor.authorMacko, Antoni R
dc.contributor.authorLynch, Ronald M
dc.contributor.authorLimesand, Sean W
dc.date.accessioned2017-04-21T23:14:24Z
dc.date.available2017-04-21T23:14:24Z
dc.date.issued2017-02
dc.identifier.citationIslet adaptations in fetal sheep persist following chronic exposure to high norepinephrine. 2017, 232 (2):285-295 J. Endocrinol.en
dc.identifier.issn1479-6805
dc.identifier.pmid27888197
dc.identifier.doi10.1530/JOE-16-0445
dc.identifier.urihttp://hdl.handle.net/10150/623222
dc.description.abstractComplications in pregnancy elevate fetal norepinephrine (NE) concentrations. Previous studies in NE-infused sheep fetuses revealed that sustained exposure to high NE resulted in lower expression of α2-adrenergic receptors in islets and increased insulin secretion responsiveness after acutely terminating the NE infusion. In this study, we determined if the compensatory increase in insulin secretion after chronic elevation of NE is independent of hyperglycemia in sheep fetuses and whether it is persistent in conjunction with islet desensitization to NE. After an initial assessment of glucose-stimulated insulin secretion (GSIS) at 129 ± 1 days of gestation, fetuses were continuously infused for seven days with NE and maintained at euglycemia with a maternal insulin infusion. Fetal GSIS studies were performed again on days 8 and 12. Adrenergic sensitivity was determined in pancreatic islets collected at day 12. NE infusion increased (P < 0.01) fetal plasma NE concentrations and lowered (P < 0.01) basal insulin concentrations compared to vehicle-infused controls. GSIS was 1.8-fold greater (P < 0.05) in NE-infused fetuses compared to controls at both one and five days after discontinuing the infusion. Glucose-potentiated arginine-induced insulin secretion was also enhanced (P < 0.01) in NE-infused fetuses. Maximum GSIS in islets isolated from NE-infused fetuses was 1.6-fold greater (P < 0.05) than controls, but islet insulin content and intracellular calcium signaling were not different between treatments. The half-maximal inhibitory concentration for NE was 2.6-fold greater (P < 0.05) in NE-infused islets compared to controls. These findings show that chronic NE exposure and not hyperglycemia produce persistent adaptations in pancreatic islets that augment β-cell responsiveness in part through decreased adrenergic sensitivity.
dc.description.sponsorshipNational Institute of Health [R01DK084842]; National Natural Science Foundation of China (NSFC) [31602021]; Chongqing Science and Technology Commission, Chongqing, China [CSTC2014JCYJA80036]; Southwest University [20140090]; [T32HL7249]en
dc.language.isoenen
dc.publisherBIOSCIENTIFICA LTDen
dc.rights© 2017 Society for Endocrinology.en
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.subjectbeta-cellen
dc.subjectadrenergic receptoren
dc.subjectislets of Langerhansen
dc.subjectcatecholamineen
dc.subjectfetal stressen
dc.titleIslet adaptations in fetal sheep persist following chronic exposure to high norepinephrine.en
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Sch Anim & Comparat Biomed Scien
dc.contributor.departmentUniv Arizona, Dept Physiolen
dc.identifier.journalThe Journal of endocrinologyen
dc.identifier.pmcid5173394
dc.description.note12 month embargo; accepted preprint published online 25 November 2016en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal accepted manuscripten
refterms.dateFOA2018-02-01T00:00:00Z
html.description.abstractComplications in pregnancy elevate fetal norepinephrine (NE) concentrations. Previous studies in NE-infused sheep fetuses revealed that sustained exposure to high NE resulted in lower expression of α2-adrenergic receptors in islets and increased insulin secretion responsiveness after acutely terminating the NE infusion. In this study, we determined if the compensatory increase in insulin secretion after chronic elevation of NE is independent of hyperglycemia in sheep fetuses and whether it is persistent in conjunction with islet desensitization to NE. After an initial assessment of glucose-stimulated insulin secretion (GSIS) at 129 ± 1 days of gestation, fetuses were continuously infused for seven days with NE and maintained at euglycemia with a maternal insulin infusion. Fetal GSIS studies were performed again on days 8 and 12. Adrenergic sensitivity was determined in pancreatic islets collected at day 12. NE infusion increased (P < 0.01) fetal plasma NE concentrations and lowered (P < 0.01) basal insulin concentrations compared to vehicle-infused controls. GSIS was 1.8-fold greater (P < 0.05) in NE-infused fetuses compared to controls at both one and five days after discontinuing the infusion. Glucose-potentiated arginine-induced insulin secretion was also enhanced (P < 0.01) in NE-infused fetuses. Maximum GSIS in islets isolated from NE-infused fetuses was 1.6-fold greater (P < 0.05) than controls, but islet insulin content and intracellular calcium signaling were not different between treatments. The half-maximal inhibitory concentration for NE was 2.6-fold greater (P < 0.05) in NE-infused islets compared to controls. These findings show that chronic NE exposure and not hyperglycemia produce persistent adaptations in pancreatic islets that augment β-cell responsiveness in part through decreased adrenergic sensitivity.


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