Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity
Pancreatic β-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. β-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:50b393711df249ed8ab6d9d9ee96364a2021-11-04T08:24:35ZOxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity1664-322410.3389/fimmu.2021.690379https://doaj.org/article/50b393711df249ed8ab6d9d9ee96364a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.690379/fullhttps://doaj.org/toc/1664-3224Pancreatic β-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. β-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are associated with pro-inflammatory conditions at the onset of the disease. Here, we investigated the effects of hydrogen peroxide-induced oxidative stress on human β-cells. We show that primary human β-cell function is decreased. This reduced function is associated with an ER stress response and the shuttling of FOXO1 to the nucleus. Furthermore, oxidative stress leads to loss of β-cell maturity genes MAFA and PDX1, and to a concomitant increase in progenitor marker expression of SOX9 and HES1. Overall, we propose that oxidative stress-induced β-cell failure may result from partial dedifferentiation. Targeting antioxidant mechanisms may preserve functional β-cell mass in early stages of development of T1D.Floris LeendersNathalie GroenNatascha de GraafMarten A. EngelseTon J. RabelinkEelco J. P. de KoningEelco J. P. de KoningFrançoise CarlottiFrontiers Media S.A.articleoxidative stressbeta-cell dysfunctionbeta-cell identitybeta-cell dedifferentiationtype 1 diabetes mellitus (T1D)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
oxidative stress beta-cell dysfunction beta-cell identity beta-cell dedifferentiation type 1 diabetes mellitus (T1D) Immunologic diseases. Allergy RC581-607 |
| spellingShingle |
oxidative stress beta-cell dysfunction beta-cell identity beta-cell dedifferentiation type 1 diabetes mellitus (T1D) Immunologic diseases. Allergy RC581-607 Floris Leenders Nathalie Groen Natascha de Graaf Marten A. Engelse Ton J. Rabelink Eelco J. P. de Koning Eelco J. P. de Koning Françoise Carlotti Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity |
| description |
Pancreatic β-cell failure is a critical event in the onset of both main types of diabetes mellitus but underlying mechanisms are not fully understood. β-cells have low anti-oxidant capacity, making them more susceptible to oxidative stress. In type 1 diabetes (T1D), reactive oxygen species (ROS) are associated with pro-inflammatory conditions at the onset of the disease. Here, we investigated the effects of hydrogen peroxide-induced oxidative stress on human β-cells. We show that primary human β-cell function is decreased. This reduced function is associated with an ER stress response and the shuttling of FOXO1 to the nucleus. Furthermore, oxidative stress leads to loss of β-cell maturity genes MAFA and PDX1, and to a concomitant increase in progenitor marker expression of SOX9 and HES1. Overall, we propose that oxidative stress-induced β-cell failure may result from partial dedifferentiation. Targeting antioxidant mechanisms may preserve functional β-cell mass in early stages of development of T1D. |
| format |
article |
| author |
Floris Leenders Nathalie Groen Natascha de Graaf Marten A. Engelse Ton J. Rabelink Eelco J. P. de Koning Eelco J. P. de Koning Françoise Carlotti |
| author_facet |
Floris Leenders Nathalie Groen Natascha de Graaf Marten A. Engelse Ton J. Rabelink Eelco J. P. de Koning Eelco J. P. de Koning Françoise Carlotti |
| author_sort |
Floris Leenders |
| title |
Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity |
| title_short |
Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity |
| title_full |
Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity |
| title_fullStr |
Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity |
| title_full_unstemmed |
Oxidative Stress Leads to β-Cell Dysfunction Through Loss of β-Cell Identity |
| title_sort |
oxidative stress leads to β-cell dysfunction through loss of β-cell identity |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/50b393711df249ed8ab6d9d9ee96364a |
| work_keys_str_mv |
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