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Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes
BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the cont...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137212/ https://www.ncbi.nlm.nih.gov/pubmed/35619086 http://dx.doi.org/10.1186/s12902-022-01033-3 |
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author | Kawoosa, Fizalah Shah, Zafar A. Masoodi, Shariq R. Amin, Asif Rasool, Roohi Fazili, Khalid M. Dar, Abid Hamid Lone, Asif ul Bashir, Samir |
author_facet | Kawoosa, Fizalah Shah, Zafar A. Masoodi, Shariq R. Amin, Asif Rasool, Roohi Fazili, Khalid M. Dar, Abid Hamid Lone, Asif ul Bashir, Samir |
author_sort | Kawoosa, Fizalah |
collection | PubMed |
description | BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. RESULTS: We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-022-01033-3. |
format | Online Article Text |
id | pubmed-9137212 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91372122022-05-28 Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes Kawoosa, Fizalah Shah, Zafar A. Masoodi, Shariq R. Amin, Asif Rasool, Roohi Fazili, Khalid M. Dar, Abid Hamid Lone, Asif ul Bashir, Samir BMC Endocr Disord Research BACKGROUND: Organic cation transporter 1 primarily governs the action of metformin in the liver. There are considerable inter-individual variations in metformin response. In light of this, it is crucial to obtain a greater understanding of the influence of OCT1 expression or polymorphism in the context of variable responses elicited by metformin treatment. RESULTS: We observed that the variable response to metformin in the responders and non-responders is independent of isoform variation and mRNA expression of OCT-1. We also observed an insignificant difference in the serum metformin levels of the patient groups. Further, molecular docking provided us with an insight into the hotspot regions of OCT-1 for metformin binding. Genotyping of these regions revealed SNPs 156T>C and 1222A>G in both the groups, while as 181C>T and 1201G>A were found only in non-responders. The 181T>C and 1222A>G changes were further found to alter OCT-1 structure in silico and affect metformin transport in vitro which was illustrated by their effect on the activation of AMPK, the marker for metformin activity. CONCLUSION: Taken together, our results corroborate the role of OCT-1 in the transport of metformin and also point at OCT1 genetic variations possibly affecting the transport of metformin into the cells and hence its subsequent action in responders and non-responders. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-022-01033-3. BioMed Central 2022-05-26 /pmc/articles/PMC9137212/ /pubmed/35619086 http://dx.doi.org/10.1186/s12902-022-01033-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Kawoosa, Fizalah Shah, Zafar A. Masoodi, Shariq R. Amin, Asif Rasool, Roohi Fazili, Khalid M. Dar, Abid Hamid Lone, Asif ul Bashir, Samir Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes |
title | Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes |
title_full | Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes |
title_fullStr | Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes |
title_full_unstemmed | Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes |
title_short | Role of human organic cation transporter-1 (OCT-1/SLC22A1) in modulating the response to metformin in patients with type 2 diabetes |
title_sort | role of human organic cation transporter-1 (oct-1/slc22a1) in modulating the response to metformin in patients with type 2 diabetes |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137212/ https://www.ncbi.nlm.nih.gov/pubmed/35619086 http://dx.doi.org/10.1186/s12902-022-01033-3 |
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