Department of Food and Biotechnology, Korea University, Sejong, South Korea.
School of Human Environmental Sciences, University of Arkansas, Fayetteville, AR, USA.
Mol Nutr Food Res. 2018 Mar;62(5). doi: 10.1002/mnfr.201700810. Epub 2018 Feb 5.
Oxidative stress has been suggested to play a central role in the pathogenesis of diabetes, as well as other metabolic disorders. Naringin, a major flavanone glycoside in citrus species, has been shown to display strong antioxidant potential in in vitro and in vivo models of oxidative stress; however, the underlying protective mechanisms in diabetes are unclear.
To study the protective effects and molecular mechanisms of naringin in preventing islet dysfunction and diabetes, we examined glucose homeostasis, β-cell apoptosis, and inflammatory response in insulin-deficient diabetic mice exposed to acute oxidative stress with streptozotocin (STZ). Naringin dose-dependently ameliorated hyperglycemia and islet dysfunction in insulin-deficient diabetic mice. Naringin counteracted STZ-induced β-cell apoptosis by inhibiting both the intrinsic (mitochondria-mediated) and extrinsic (death receptor-mediated) pathways. Furthermore, these protective effects were associated with suppression of DNA damage response and nuclear factor-kappa B- and mitogen-activated protein kinase-mediated signaling pathways, as well as reduction of reactive oxygen species accumulation and pro-inflammatory cytokine production in the pancreas.
Taken together, our study provides insights into the underlying mechanisms through which naringin protects the pancreatic β-cells against oxidative stress-induced apoptosis.
氧化应激被认为在糖尿病以及其他代谢紊乱的发病机制中起着核心作用。柚皮苷是柑橘类水果中的主要类黄酮糖苷，已在体外和体内氧化应激模型中显示出强大的抗氧化潜力；然而，糖尿病中潜在的保护机制尚不清楚。
为了研究柚皮苷在预防胰岛功能障碍和糖尿病中的保护作用和分子机制，我们研究了暴露于链脲佐菌素（STZ）急性氧化应激下的胰岛素缺乏型糖尿病小鼠的葡萄糖稳态、β细胞凋亡和炎症反应。柚皮苷剂量依赖性地改善了胰岛素缺乏型糖尿病小鼠的高血糖和胰岛功能障碍。柚皮苷通过抑制内在（线粒体介导）和外在（死亡受体介导）途径来拮抗 STZ 诱导的β细胞凋亡。此外，这些保护作用与抑制 DNA 损伤反应以及核因子-κB 和丝裂原激活蛋白激酶介导的信号通路有关，同时还减少了胰腺中活性氧物质的积累和促炎细胞因子的产生。
综上所述，我们的研究深入了解了柚皮苷保护胰腺β细胞免受氧化应激诱导的细胞凋亡的潜在机制。
