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Metformin, empagliflozin and their combination modulate ex-vivo macrophage inflammatory gene expression

View ORCID ProfileAdittya Arefin, View ORCID ProfileMatthew C. Gage
doi: https://doi.org/10.1101/2022.06.20.496771
Adittya Arefin
1Wolfson Institute for Biomedical Research, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, United Kingdom
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Matthew C. Gage
2Department of Comparative Biomedical Sciences, Royal Veterinary College, 4 Royal College Street, London NW1 0TU, United Kingdom
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  • For correspondence: mgage@rvc.ac.uk
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Abstract

Type-2 Diabetes Mellitus is a complex, chronic illness characterized by persistent high blood glucose levels. Patients can be prescribed anti-diabetes drugs as single agents or in combination depending on the severity of their condition. Metformin and empagliflozin are two commonly prescribed anti-diabetes drugs which reduce hyperglycemia, however their direct effects on macrophage inflammatory responses alone or in combination are unreported. Here we show that metformin and empagliflozin elicit proinflammatory responses on mouse bone-marrow derived macrophages with single agent challenge, which are modulated when added in combination. In-silico docking experiments suggested that empagliflozin can interact with both TLR2 and DECTIN1 receptors and we observed that both empagliflozin and metformin increase expression of Tlr2 and Clec7a. Thus, findings from this study suggest that metformin and empagliflozin as single agents or in combination can directly modulate inflammatory gene expression in macrophages and upregulate the expression of their receptors.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 20, 2022.
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Metformin, empagliflozin and their combination modulate ex-vivo macrophage inflammatory gene expression
Adittya Arefin, Matthew C. Gage
bioRxiv 2022.06.20.496771; doi: https://doi.org/10.1101/2022.06.20.496771
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Metformin, empagliflozin and their combination modulate ex-vivo macrophage inflammatory gene expression
Adittya Arefin, Matthew C. Gage
bioRxiv 2022.06.20.496771; doi: https://doi.org/10.1101/2022.06.20.496771

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