State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China.
Evid Based Complement Alternat Med. 2013;2013:303902. doi: 10.1155/2013/303902. Epub 2013 Feb 27.
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.
果糖诱导的高胰岛素血症与胰岛素代偿性分泌有关，并可预测 2 型糖尿病的发生。在这项研究中，我们研究了饮食类黄酮槲皮素对果糖处理大鼠和 INS-1β细胞中胰岛β细胞质量和功能的保护作用。槲皮素可降低血清胰岛素和瘦素水平，并阻断果糖喂养大鼠胰岛增生。它还可防止果糖诱导的 INS-1β细胞中β细胞增殖和胰岛素分泌过多。高果糖可增加体内和体外 FoxO1（叉头框蛋白 O1）的表达，而槲皮素可逆转这种作用。在果糖喂养的大鼠胰岛中，槲皮素下调 Akt 和 FoxO1磷酸化，并增加果糖处理的 INS-1β细胞中的核 FoxO1水平。在果糖处理的 INS-1β细胞中，Akt 磷酸化也被槲皮素恢复。此外，槲皮素可抑制体内和体外胰腺十二指肠同源盒 1（Pdx1）和胰岛素基因（Ins1 和 Ins2）的表达。在果糖处理的 INS-1β细胞中，槲皮素升高了降低的 Janus 激酶 2/信号转导子和转录激活子 3（Jak2/Stat3）磷酸化，并抑制了增加的细胞因子信号转导抑制物 3（Socs3）表达。这些结果表明，槲皮素通过改善瘦素信号和维持胰腺 Akt/FoxO1 激活，在高果糖诱导下保护β细胞质量和功能。
