Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering (MBBE), College of Tropical Agriculture and Human Resources (CTAHR), University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Retrovirology Research Laboratory, Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96813, USA.
Br J Nutr. 2012 Jul;108(2):218-228. doi: 10.1017/S0007114511005563. Epub 2011 Oct 20.
Renewed interest in alternative medicine among diabetic individuals prompted us to investigate anti-diabetic effects of Morinda citrifolia (noni) in high-fat diet (HFD)-fed mice. Type 2 diabetes is associated with increased glucose production due to the inability of insulin to suppress hepatic gluconeogenesis and promote glycolysis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Based on microarray analysis data, we tested the hypothesis that fermented noni fruit juice (fNJ) improves glucose metabolism via FoxO1 phosphorylation. C57BL/6 male mice were fed a HFD and fNJ for 12 weeks. Body weights and food intake were monitored daily. FoxO1 expression was analysed by real-time PCR and Western blotting. Specificity of fNJ-associated FoxO1 regulation of gluconeogenesis was confirmed by small interfering RNA (siRNA) studies using human hepatoma cells, HepG2. Supplementation with fNJ inhibited weight gain and improved glucose and insulin tolerance and fasting glucose in HFD-fed mice. Hypoglycaemic properties of fNJ were associated with the inhibition of hepatic FoxO1 mRNA expression, with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion of the proteins. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose-6-phosphatase (G6P), were significantly inhibited in mice fed a HFD+fNJ. HepG2 cells demonstrated more than 80 % inhibition of PEPCK and G6P mRNA expression in cells treated with FoxO1 siRNA and fNJ. These data suggest that fNJ improves glucose metabolism via FoxO1 regulation in HFD-fed mice.
对糖尿病患者中替代医学的兴趣再次兴起，促使我们研究了诺丽果（noni）对高脂肪饮食（HFD）喂养的小鼠的降血糖作用。2 型糖尿病与葡萄糖生成增加有关，这是由于胰岛素无法抑制肝糖异生和促进糖酵解。胰岛素通过调节叉头框 O（FoxO1）等转录因子来抑制糖异生。基于微阵列分析数据，我们测试了发酵诺丽果汁（fNJ）通过 FoxO1 磷酸化改善葡萄糖代谢的假设。C57BL/6 雄性小鼠喂食 HFD 和 fNJ 共 12 周。每天监测体重和食物摄入量。通过实时 PCR 和 Western blot 分析 FoxO1 表达。使用人肝癌细胞 HepG2 通过小干扰 RNA（siRNA）研究证实了 fNJ 相关的 FoxO1 对糖异生的调节的特异性。fNJ 的补充抑制了 HFD 喂养小鼠的体重增加，改善了葡萄糖和胰岛素耐量以及空腹血糖。fNJ 的降血糖作用与抑制肝 FoxO1 mRNA 表达有关，同时 FoxO1 磷酸化增加，蛋白核外排出。在喂食 HFD+fNJ 的小鼠中，糖异生基因磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6P）显著受到抑制。FoxO1 siRNA 和 fNJ 处理的 HepG2 细胞中，PEPCK 和 G6P mRNA 表达抑制超过 80%。这些数据表明，fNJ 通过 HFD 喂养小鼠的 FoxO1 调节改善葡萄糖代谢。
