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.