Insulin‐Sensitizing Activity of Sub‐Nanoscaled Polyalkoxyvanadate Clusters

Abstract

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.

Surface Engineering Promoted Insulin‐Sensitizing Activities of Sub‐Nanoscale Vanadate Clusters through Regulated Pharmacokinetics and Bioavailability

“…Consistent with our previous work, POV-fed diabetic rats showed lower glucose levels [32] in serum than PBS-fed rats in an intraperitoneal glucose tolerance test (IPGTT, Figure 4). The insulin-sensitizing activity of POVs becomes notable with the extension of alkyl chains, which have a significant impact on POV absorption and clearance.…”

“…These POVs are highly size-and composition-tunable at the atomic scale. Modification by organic ligands can fine-tune the size and the properties of POVs, [29][30][31][32][33] which determines the pharmacokinetic properties of POVs. POVs are covalently capped with alkoxy ligands, thus they are much more structurally stable to obtain their pharmacokinetic parameters from the experiment and to investigate the effect of surface engineering on the preclinical pharmacokinetics of these sub-nanoscale metal oxide clusters.…”

“…To fine-tune the cluster size and hydrophobicity, various functional groups can be grafted on the POV surface facilely via typical esterification and amidation protocols. [32,33] The rich chemical modification of POVs promotes the shift from simply trial-and-error to the rational design of POVs with desirable biochemical and physiological activities. In this work, the sodium salts of the functionalized POVs are investigated for their promising solubility in aqueous media, including Na 1A shows the rough size of the synthesized POVs with sizes ranging from 0.8 × 1.2 (V6-OH) to 1.6 × 5.6 nm (V6-C18).…”

“…Each vanadium atom is captured and stabilized by the tris(alkoxo) bridging ligands, resulting in the enhanced structural stability of the cluster. [29][30][31][32][33][34][35][36] Together, compared with pure inorganic POVs, such as V10, surface engineering significantly reduces POV variation in species and enhances their stability in biological fluids.…”

Degradation and Detection of Endocrine Disruptors by Laccase-Mimetic Polyoxometalates

“…At the same time, POM surfaces are rich in oxygen, hydroxyl, and/or water ligands, suggesting that POM-based materials are excellent candidates for biomimetic applications. Over the last decades, POMs have demonstrated their promising biological activities, such as antitumoral ( Bijelic et al, 2019 ), antimicrobial ( Xu et al, 2020 ; Chen et al, 2021 ; Chen et al, 2022 ), insulin-sensitizing ( Chen et al, 2020 ), immune-enhancing activities ( Li et al, 2021 ; Li et al, 2022 ). In virtue of their structural diversity and physicochemical properties, POM-based nanomaterials exert oxidoreductase-mimicking activities, including oxidase, peroxidase ( Chen K. et al, 2018 ; Jia et al, 2019 ), and catalase ( Yadav and Singh, 2021 ).…”