New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform

Rokon Uddin, N. Nur-E-Habiba, Graham Rena, En Te Hwu, Anja Boisen

    Research output: Contribution to journalArticleScientificpeer-review

    9 Citations (Scopus)

    Abstract

    The mechanism of action (MOA) of the first line type-2 diabetes drug metformin remains unclear despite its widespread usage. However, recent evidence suggests that the mitochondrial copper (Cu)-binding action of metformin may contribute toward the drug's MOA. Here, we present a novel biosensing platform for investigating the MOA of metformin using a magnetic microbead-based agglutination assay which has allowed us to demonstrate for the first time the interaction between Cu and metformin at clinically relevant low micromolar concentrations of the drug, thus suggesting a potential pathway of metformin's blood-glucose lowering action. In this assay, cysteine-functionalized magnetic beadswere agglutinated in the presence of Cu due to cysteine's Cu-chelation property. Addition of clinically relevant doses of metformin resulted in disaggregation of Cu-bridged bead-clusters, whereas the effect of adding a closely related but blood-glucose neutral drug propanediimidamide (PDI) showed completely different responses to the clusters. The entire assay was integrated in an automated microfluidics platform with an advanced optical imaging unit by which we investigated these aggregation-disaggregation phenomena in a reliable, automated, and user-friendly fashion with total assay time of 17 min requiring a sample (metformin/PDI) volume of 30 μL. The marked difference of Cu-binding action between the blood-glucose lowering drug metformin and its inactive analogue PDI thus suggests that metformin's distinctive Cu-binding properties may be required for its effect on glucose homeostasis. The novel automated platform demonstrating this novel investigation thus holds the potential to be utilized for investigating significant and sensitive molecular interactions via magnetic bead-based agglutination assay.

    Original languageEnglish
    Pages (from-to)1329-1336
    Number of pages8
    JournalACS Sensors
    Volume2
    Issue number9
    DOIs
    Publication statusPublished - 22 Sept 2017
    Publication typeA1 Journal article-refereed

    Keywords

    • agglutination assay
    • biosensor
    • magnetic beads
    • metformin
    • molecular interactions
    • optical imaging
    • type-2 diabetes

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Bioengineering
    • Fluid Flow and Transfer Processes
    • Process Chemistry and Technology
    • Instrumentation

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