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dc.contributor.authorNguyen-Ngo, C
dc.contributor.authorSalomon, C
dc.contributor.authorQuak, S
dc.contributor.authorLai, A
dc.contributor.authorWillcox, JC
dc.contributor.authorLappas, M
dc.date.accessioned2020-11-26T22:50:16Z
dc.date.available2020-11-26T22:50:16Z
dc.date.issued2020-03-01
dc.identifierpii: 222287
dc.identifier.citationNguyen-Ngo, C., Salomon, C., Quak, S., Lai, A., Willcox, J. C. & Lappas, M. (2020). Nobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes. CLINICAL SCIENCE, 134 (6), pp.571-592. https://doi.org/10.1042/CS20191099.
dc.identifier.issn0143-5221
dc.identifier.urihttp://hdl.handle.net/11343/252009
dc.description.abstractGestational diabetes mellitus (GDM) is a global health issue, whereby pregnant women are afflicted with carbohydrate intolerance with first onset during pregnancy. GDM is characterized by maternal peripheral insulin resistance, thought to be driven by low-grade maternal inflammation. Nobiletin, a polymethoxylated flavonoid, possesses potent glucose-sensitizing and anti-inflammatory properties; however, its effects in GDM have not been assessed. The present study aimed to determine the effects of nobiletin on glucose metabolism and inflammation associated with GDM in both in vitro human tissues and an in vivo animal model of GDM. In vitro, treatment with nobiletin significantly improved TNF-impaired glucose uptake in human skeletal muscle, and suppressed mRNA expression and protein secretion of pro-inflammatory cytokines and chemokines in human placenta and visceral adipose tissue (VAT). Mechanistically, nobiletin significantly inhibited Akt and Erk activation in placenta, and NF-κB activation in VAT. In vivo, GDM mice treated with 50 mg/kg nobiletin daily via oral gavage from gestational day (gd) 1-17 or via i.p. injections from gd 10-17 significantly improved glucose tolerance. Pregnant GDM mice treated with nobiletin from either gd 1-17 or gd 10-17 exhibited significantly suppressed mRNA expression of pro-inflammatory cytokines and chemokines in placenta, VAT and subcutaneous adipose tissue (SAT). Using a quantitative mass spectrometry approach, we identified differentially abundant proteins associated with the effect of nobiletin in vivo. Together, these studies demonstrate that nobiletin improves glucose metabolism and reduces inflammation associated with GDM and may be a novel therapeutic for the prevention of GDM.
dc.languageEnglish
dc.publisherPORTLAND PRESS LTD
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleNobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes
dc.typeJournal Article
dc.identifier.doi10.1042/CS20191099
melbourne.affiliation.departmentObstetrics and Gynaecology
melbourne.affiliation.department
melbourne.source.titleClinical Science
melbourne.source.volume134
melbourne.source.issue6
melbourne.source.pages571-592
dc.rights.licensecc-by-nc-nd
melbourne.elementsid1441111
melbourne.contributor.authorLappas, Martha
melbourne.contributor.authorNguyen-Ngo, Caitlyn
melbourne.contributor.authorQUAK, STEPHANIE
dc.identifier.eissn1470-8736
melbourne.accessrightsOpen Access


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