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Identification of Probucol as a candidate for combination therapy with Metformin for Type 2 diabetes

Guttapadu, R and Korla, K and Uk, S and Annam, V and Ashok, P and Chandra, N (2023) Identification of Probucol as a candidate for combination therapy with Metformin for Type 2 diabetes. In: npj Systems Biology and Applications, 9 (1).

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Official URL: https://doi.org/10.1038/s41540-023-00275-8


Type 2 Diabetes (T2D) is often managed with metformin as the drug of choice. While it is effective overall, many patients progress to exhibit complications. Strategic drug combinations to tackle this problem would be useful. We constructed a genome-wide protein-protein interaction network capturing a global perspective of perturbations in diabetes by integrating T2D subjects’ transcriptomic data. We computed a ‘frequently perturbed subnetwork’ in T2D that captures common perturbations across tissue types and mapped the possible effects of Metformin onto it. We then identified a set of remaining T2D perturbations and potential drug targets among them, related to oxidative stress and hypercholesterolemia. We then identified Probucol as the potential co-drug for adjunct therapy with Metformin and evaluated the efficacy of the combination in a rat model of diabetes. We find Metformin-Probucol at 5:0.5 mg/kg effective in restoring near-normal serum glucose, lipid, and cholesterol levels.

Item Type: Journal Article
Publication: npj Systems Biology and Applications
Publisher: Nature Research
Additional Information: The copyright for this article belongs to the author.
Keywords: metformin; probucol, animal; gene expression profiling; non insulin dependent diabetes mellitus; oxidative stress; rat, Animals; Diabetes Mellitus, Type 2; Gene Expression Profiling; Metformin; Oxidative Stress; Probucol; Rats
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 09 Jul 2023 17:33
Last Modified: 09 Jul 2023 17:33
URI: https://eprints.iisc.ac.in/id/eprint/82075

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