Biological Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India; Academy of Scientific and Innovative Research, Chennai, India.
Clinical Centre, CSIR-North East Institute of Science and Technology, Jorhat, Assam, India.
J Nutr Biochem. 2018 Feb;52:103-114. doi: 10.1016/j.jnutbio.2017.09.022. Epub 2017 Oct 12.
There is no previous study in the literature that has examined the relationship between circulating vitamin K1 (VK1) with glycemic status in type 2 diabetes (T2D). Moreover, scientific explanation for the beneficial role of VK1 supplementation in lowering glycemia in diabetes is yet to be determined. This study for the first time demonstrated that circulating VK1 was significantly lower in T2D patients compared to age-matched control subjects, and VK1 levels in T2D were significantly and inversely associated with fasting glucose and insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR)], which suggest that boosting plasma VK1 may reduce the fasting glucose and insulin resistance in T2D patients. Using high-fat-diet-fed T2D animal model, this study further investigated the positive effect of VK1 supplementation on glucose metabolism and examined the underlying molecular mechanism. Results showed that VK1 supplementation [1, 3, 5 μg/kg body weight (BW), 8 weeks] dose dependently improved the glucose tolerance; decreased BW gain, fasting glucose and insulin, glycated hemoglobin, HOMA-IR and cytokine secretion (monocyte chemoattractant protein-1 and interleukin-6); and regulated the signaling pathway of hepatic glucose metabolism [sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK)/phosphoinositide 3-kinase/phosphatase and tensin homolog/glucose transporter 2/glucokinase/glucose 6 phosphatase], lipid oxidation (peroxisome proliferator-activated receptor alpha/carnitine palmitoyltransferase 1A) and inflammation (nuclear factor kappa B) in T2D mice. Comparative signal silencing studies also depicted the role of SIRT1/AMPK in mediating the effect of VK1 on glucose metabolism, lipid oxidation and inflammation in high-glucose-treated cultured hepatocytes. In conclusion, this study demonstrates that circulating VK1 has a positive effect on lowering fasting glucose and insulin resistance in T2D via regulating SIRT1/AMPK signaling pathway.
目前文献中尚无研究探讨 2 型糖尿病（T2D）患者循环维生素 K1（VK1）与血糖状态之间的关系。此外，VK1 补充剂降低糖尿病患者血糖的有益作用的科学解释仍有待确定。本研究首次表明，与年龄匹配的对照组相比，T2D 患者的循环 VK1 水平明显降低，T2D 患者的 VK1 水平与空腹血糖和胰岛素抵抗[胰岛素抵抗稳态模型评估（HOMA-IR）]呈显著负相关，这表明提高血浆 VK1 水平可能降低 T2D 患者的空腹血糖和胰岛素抵抗。本研究使用高脂肪饮食喂养的 T2D 动物模型，进一步研究了 VK1 补充对葡萄糖代谢的积极影响，并检查了潜在的分子机制。结果表明，VK1 补充[1、3、5μg/kg 体重（BW），8 周]剂量依赖性地改善了葡萄糖耐量；降低了 BW 增加、空腹血糖和胰岛素、糖化血红蛋白、HOMA-IR 和细胞因子分泌（单核细胞趋化蛋白-1 和白细胞介素-6）；并调节了肝葡萄糖代谢的信号通路[沉默调节蛋白 1（SIRT1）/AMP 激活的蛋白激酶（AMPK）/磷酸肌醇 3-激酶/张力蛋白同源物/葡萄糖转运体 2/葡萄糖激酶/葡萄糖 6 磷酸酶]、脂质氧化（过氧化物酶体增殖物激活受体α/肉碱棕榈酰转移酶 1A）和炎症（核因子 kappa B）在 T2D 小鼠中。比较信号沉默研究还描绘了 SIRT1/AMPK 在介导 VK1 对高葡萄糖处理培养的肝细胞中葡萄糖代谢、脂质氧化和炎症的作用。总之，本研究表明，循环 VK1 通过调节 SIRT1/AMPK 信号通路对降低 T2D 的空腹血糖和胰岛素抵抗具有积极作用。
