Kun Chen, Hongli Jia, Yuan Liu, Panchao Yin,* and Yongge Wei*

  Sub‐nanoscaled polyalkoxyvanadates (PAOVs) functionalized with various aliphatic acids are evaluated for their insulin‐sensitizing activity in lowering the blood glucose levels of diabetic mice in typical glucose tolerance tests. All the PAOVs can restore the blood glucose to normal levels after a single oral administration of PAOVs. Among them, the myristic acid‐modified PAOVs enable the response of insulin to the repeated glucose challenges, lasting for up to 13 h. The combined administration of PAOVs exerts better glucose control over insulin alone, while the capric acid‐ and myristic acid‐modified ones can enhance the responsiveness of insulin to glucose challenge and is comparable to a clinical‐used derivative of insulin. Interestingly, continuous glucose monitoring shows that myristic acid‐modified PAOV derivatives sensitize the responsiveness of insulin, almost matching with that of a healthy pancreas. These discoveries open up new opportunities for the application of PAOVs to promote glucose‐responsive and long‐lasting activity of insulin, which are expected to aid the accurate blood glucose control in insulin therapy while reducing the number of insulin administrations.

    在典型的糖耐量试验中，我们评估了不同脂族酸功能化的亚纳米级多钒酸盐烷氧衍生物(PAOVs)在降低糖尿病小鼠血糖水平中的胰岛素增敏活性。口服一次PAOVs后，所有PAOVs均能使血糖恢复到正常水平。其中，肉豆蔻酸修饰的PAOVs可使胰岛素对重复的葡萄糖耐量做出反应，持续长达13小时。联合使用PAOVs可更好地单独控制胰岛素的血糖，而癸酸和肉豆蔻酸修饰的PAOVs可增强胰岛素对葡萄糖耐量的反应性，可与临床使用的胰岛素衍生物相媲美。有趣的是，持续的血糖监测显示，肉豆蔻酸修饰的PAOV衍生物对胰岛素的敏感性几乎与健康的胰腺相当。这些发现为PAOVs在促进胰岛素的葡萄糖响应性和长效活性的应用提供了新的机会，这将有助于在胰岛素治疗中准确控制血糖，同时减少胰岛素的使用次数。

Keywords: alkyl chain‐modification  insulin-sensitizing activity  polyalkoxyvanadates  sub-nanoclusters

文章链接：https://onlinelibrary.wiley.com/doi/10.1002/adbi.201900281