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

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New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform. / Uddin, Rokon; Nur-E-Habiba, N.; Rena, Graham; Hwu, En Te; Boisen, Anja.

julkaisussa: ACS Sensors, Vuosikerta 2, Nro 9, 22.09.2017, s. 1329-1336.

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Uddin, R, Nur-E-Habiba, N, Rena, G, Hwu, ET & Boisen, A 2017, 'New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform', ACS Sensors, Vuosikerta. 2, Nro 9, Sivut 1329-1336. https://doi.org/10.1021/acssensors.7b00384

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Author

Uddin, Rokon ; Nur-E-Habiba, N. ; Rena, Graham ; Hwu, En Te ; Boisen, Anja. / New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform. Julkaisussa: ACS Sensors. 2017 ; Vuosikerta 2, Nro 9. Sivut 1329-1336.

Bibtex - Lataa

@article{1d658c5033984e2883c0c84173d6dfee,
title = "New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform",
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.",
keywords = "agglutination assay, biosensor, magnetic beads, metformin, molecular interactions, optical imaging, type-2 diabetes",
author = "Rokon Uddin and N. Nur-E-Habiba and Graham Rena and Hwu, {En Te} and Anja Boisen",
note = "INT=keb,{"}Nur-E-Habiba, N.{"}",
year = "2017",
month = "9",
day = "22",
doi = "10.1021/acssensors.7b00384",
language = "English",
volume = "2",
pages = "1329--1336",
journal = "Sensors",
issn = "1424-8220",
publisher = "MDPI",
number = "9",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - New Evidence for the Mechanism of Action of a Type-2 Diabetes Drug Using a Magnetic Bead-Based Automated Biosensing Platform

AU - Uddin, Rokon

AU - Nur-E-Habiba, N.

AU - Rena, Graham

AU - Hwu, En Te

AU - Boisen, Anja

N1 - INT=keb,"Nur-E-Habiba, N."

PY - 2017/9/22

Y1 - 2017/9/22

N2 - 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.

AB - 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.

KW - agglutination assay

KW - biosensor

KW - magnetic beads

KW - metformin

KW - molecular interactions

KW - optical imaging

KW - type-2 diabetes

U2 - 10.1021/acssensors.7b00384

DO - 10.1021/acssensors.7b00384

M3 - Article

VL - 2

SP - 1329

EP - 1336

JO - Sensors

JF - Sensors

SN - 1424-8220

IS - 9

ER -