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Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium
Metformin is a traditional anti-hyperglycemic medication that has recently been shown to benefit vascular complications of diabetes via an anti-inflammatory mechanism other than glycemic control. This study aims to test the hypothesis that metformin suppresses diabetic retinopathy (DR) associated in...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269956/ https://www.ncbi.nlm.nih.gov/pubmed/35802672 http://dx.doi.org/10.1371/journal.pone.0268451 |
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author | Li, Yue Gappy, Shawn Liu, Xiuli Sassalos, Therese Zhou, Tongrong Hsu, Andrew Zhang, Alice Edwards, Paul A. Gao, Hua Qiao, Xiaoxi |
author_facet | Li, Yue Gappy, Shawn Liu, Xiuli Sassalos, Therese Zhou, Tongrong Hsu, Andrew Zhang, Alice Edwards, Paul A. Gao, Hua Qiao, Xiaoxi |
author_sort | Li, Yue |
collection | PubMed |
description | Metformin is a traditional anti-hyperglycemic medication that has recently been shown to benefit vascular complications of diabetes via an anti-inflammatory mechanism other than glycemic control. This study aims to test the hypothesis that metformin suppresses diabetic retinopathy (DR) associated intraocular inflammation. Human vitreous from control and proliferative diabetic retinopathy (PDR) patients with or without long-term metformin treatment (> 5 years) were collected for multiple inflammatory cytokines measurements with a cytokine array kit. The vast majority of the measurable cytokines in PDR vitreous has a lower level in metformin group than non-metformin group. Although the p values are not significant due to a relatively small sample size and large deviations, the 95% confidence interval (CI) for the mean difference between the two groups shows some difference in the true values should not be neglected. Using quantitative ELISA, soluble intercellular adhesion molecule -1 (ICAM-1) and monocyte chemoattractant protein -1 (MCP-1) presented with significantly lower concentrations in metformin group versus non-metformin group. Metformin group also has significantly less up-regulated cytokines and diminished positive correlations among the cytokines when compared to non-metformin group. Possible role of AMP-activated protein kinase (AMPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in metformin’s anti-inflammatory effects were studied in human retinal vascular endothelial cells (hRVECs) cultured in normal glucose (NG) and high glucose (HG) conditions. Metformin inhibited HG-induced ICAM-1, IL-8, and MCP-1 via AMPK activation, whereas pharmacological AMPK inhibition had no effect on its inhibition of NF-κB p65, sICAM-1, and tumor necrosis factor-α (TNF-α). Metformin-induced suppression of the inflammatory cytokines could also be mediated through its direct inhibition of NF-κB, independent of AMPK pathway. This is a proof-of-concept study that found metformin treatment was associated with reduced inflammatory responses in vitreous of diabetes patients and retinal vascular endothelial cells, supporting the rationale for using metformin to treat DR at an early stage. |
format | Online Article Text |
id | pubmed-9269956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92699562022-07-09 Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium Li, Yue Gappy, Shawn Liu, Xiuli Sassalos, Therese Zhou, Tongrong Hsu, Andrew Zhang, Alice Edwards, Paul A. Gao, Hua Qiao, Xiaoxi PLoS One Research Article Metformin is a traditional anti-hyperglycemic medication that has recently been shown to benefit vascular complications of diabetes via an anti-inflammatory mechanism other than glycemic control. This study aims to test the hypothesis that metformin suppresses diabetic retinopathy (DR) associated intraocular inflammation. Human vitreous from control and proliferative diabetic retinopathy (PDR) patients with or without long-term metformin treatment (> 5 years) were collected for multiple inflammatory cytokines measurements with a cytokine array kit. The vast majority of the measurable cytokines in PDR vitreous has a lower level in metformin group than non-metformin group. Although the p values are not significant due to a relatively small sample size and large deviations, the 95% confidence interval (CI) for the mean difference between the two groups shows some difference in the true values should not be neglected. Using quantitative ELISA, soluble intercellular adhesion molecule -1 (ICAM-1) and monocyte chemoattractant protein -1 (MCP-1) presented with significantly lower concentrations in metformin group versus non-metformin group. Metformin group also has significantly less up-regulated cytokines and diminished positive correlations among the cytokines when compared to non-metformin group. Possible role of AMP-activated protein kinase (AMPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in metformin’s anti-inflammatory effects were studied in human retinal vascular endothelial cells (hRVECs) cultured in normal glucose (NG) and high glucose (HG) conditions. Metformin inhibited HG-induced ICAM-1, IL-8, and MCP-1 via AMPK activation, whereas pharmacological AMPK inhibition had no effect on its inhibition of NF-κB p65, sICAM-1, and tumor necrosis factor-α (TNF-α). Metformin-induced suppression of the inflammatory cytokines could also be mediated through its direct inhibition of NF-κB, independent of AMPK pathway. This is a proof-of-concept study that found metformin treatment was associated with reduced inflammatory responses in vitreous of diabetes patients and retinal vascular endothelial cells, supporting the rationale for using metformin to treat DR at an early stage. Public Library of Science 2022-07-08 /pmc/articles/PMC9269956/ /pubmed/35802672 http://dx.doi.org/10.1371/journal.pone.0268451 Text en © 2022 Li et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Li, Yue Gappy, Shawn Liu, Xiuli Sassalos, Therese Zhou, Tongrong Hsu, Andrew Zhang, Alice Edwards, Paul A. Gao, Hua Qiao, Xiaoxi Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
title | Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
title_full | Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
title_fullStr | Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
title_full_unstemmed | Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
title_short | Metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
title_sort | metformin suppresses pro-inflammatory cytokines in vitreous of diabetes patients and human retinal vascular endothelium |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269956/ https://www.ncbi.nlm.nih.gov/pubmed/35802672 http://dx.doi.org/10.1371/journal.pone.0268451 |
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