Nobiletin exerts anti-diabetic and anti-inflammatory effects in an in vitro human model and in vivo murine model of gestational diabetes

Clinical Science
Caitlyn Nguyen-NgoMartha Lappas

Abstract

Gestational 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 eit...Continue Reading

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Citations

Jan 22, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guangning KouQuanjun Lyu
Feb 3, 2021·Seminars in Reproductive Medicine·Danielle A J M SchoenakerShelley Wilkinson
Mar 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Samah A El-NewaryAbdelsamed I Elshamy

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