title: Quercetin Preserves β -Cell Mass and Function in Fructose-Induced Hyperinsulinemia through Modulating Pancreatic Akt/FoxO1 Activation.
abstract: Fructose-induced hyperinsulinemia is associated with insulin compensative secretion and predicts the onset of type 2 diabetes. In this study, we investigated the preservation of dietary flavonoid quercetin on pancreatic β -cell mass and function in fructose-treated rats and INS-1 β -cells. Quercetin was confirmed to reduce serum insulin and leptin levels and blockade islet hyperplasia in fructose-fed rats. It also prevented fructose-induced β -cell proliferation and insulin hypersecretion in INS-1 β -cells. High fructose increased forkhead box protein O1 (FoxO1) expressions in vivo and in vitro, which were reversed by quercetin. Quercetin downregulated Akt and FoxO1 phosphorylation in fructose-fed rat islets and increased the nuclear FoxO1 levels in fructose-treated INS-1 β -cells. The elevated Akt phosphorylation in fructose-treated INS-1 β -cells was also restored by quercetin. Additionally, quercetin suppressed the expression of pancreatic and duodenal homeobox 1 (Pdx1) and insulin gene (Ins1 and Ins2) in vivo and in vitro. In fructose-treated INS-1 β -cells, quercetin elevated the reduced janus kinase 2/signal transducers and activators of transcription 3 (Jak2/Stat3) phosphorylation and suppressed the increased suppressor of cytokine signaling 3 (Socs3) expression. These results demonstrate that quercetin protects β -cell mass and function under high-fructose induction through improving leptin signaling and preserving pancreatic Akt/FoxO1 activation.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Fan
authors.forename: Ming-Xing
authors.initials: MX
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Hu
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong