Insulin-Sensitizing Activity of Sub-Nanoscaled Polyalkoxyvanadate Clusters.

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.