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.
Renewed interest in traditional medicine prompted us to investigate anti‐diabetic effects of Hawaiian medicinal plant, Morinda Citrifolia (noni) in mice fed high‐fat‐diet (HFD). Preliminary studies indicate that noni juice (NJ) improved glucose metabolism in mice fed HFD. Glucose production is increased in diabetes due to the inability of insulin to suppress gluconeogenesis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Since recent studies indicate that NJ synergistically augment insulin action in diabetic rats, we tested the hypothesis that NJ improves glucose metabolism by modulating gluconeogenesis via FoxO1 phosphorylation. In our studies hypoglycemic properties of NJ were associated with inhibition of hepatic FoxO1 mRNA expression and protein levels with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose‐6‐phosphatase (G6P) were also significantly inhibited in mice fed HFD with NJ. Specificity of NJ‐associated FoxO1 regulation of gluconeogenesis was confirmed by siRNA studies using human hepatoma cells, HepG2. Our data suggests that NJ can offer an economical alternative, specifically for culturally sensitive diabetic individuals or those who cannot afford conventional medicine. [USDA‐CREES, 2004‐34135‐15182; NCCAM, R21AT003719].
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