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Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans
The potential to treat diabetes by increasing beta-cell mass is driving a major effort to identify beta-cell mitogens. Demonstration of mitogen activity in human beta cells is frequently performed in ex vivo assays. However, reported disparities in the efficacy of beta-cell mitogens led us to invest...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163757/ https://www.ncbi.nlm.nih.gov/pubmed/34050242 http://dx.doi.org/10.1038/s41598-021-90643-3 |
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author | Maachi, Hasna Ghislain, Julien Tremblay, Caroline Poitout, Vincent |
author_facet | Maachi, Hasna Ghislain, Julien Tremblay, Caroline Poitout, Vincent |
author_sort | Maachi, Hasna |
collection | PubMed |
description | The potential to treat diabetes by increasing beta-cell mass is driving a major effort to identify beta-cell mitogens. Demonstration of mitogen activity in human beta cells is frequently performed in ex vivo assays. However, reported disparities in the efficacy of beta-cell mitogens led us to investigate the sources of this variability. We studied 35 male (23) and female (12) human islet batches covering a range of donor ages and BMI. Islets were kept intact or dispersed into single cells and cultured in the presence of harmine, glucose, or heparin-binding epidermal growth factor-like growth factor (HB-EGF), and subsequently analyzed by immunohistochemistry or flow cytometry. Proliferating cells were identified by double labeling with EdU and Ki67 and glucagon, c-peptide or Nkx6.1, and cytokeratin-19 to respectively label alpha, beta, and ductal cells. Harmine and HB-EGF stimulated human beta-cell proliferation, but the effect of glucose was dependent on the assay and the donor. Harmine potently stimulated alpha-cell proliferation and both harmine and HB-EGF increased proliferation of insulin- and glucagon-negative cells, including cytokeratin 19-positive cells. Given the abundance of non-beta cells in human islet preparations, our results suggest that assessment of beta-cell mitogens requires complementary approaches and rigorous identification of cell identity using multiple markers. |
format | Online Article Text |
id | pubmed-8163757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81637572021-06-01 Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans Maachi, Hasna Ghislain, Julien Tremblay, Caroline Poitout, Vincent Sci Rep Article The potential to treat diabetes by increasing beta-cell mass is driving a major effort to identify beta-cell mitogens. Demonstration of mitogen activity in human beta cells is frequently performed in ex vivo assays. However, reported disparities in the efficacy of beta-cell mitogens led us to investigate the sources of this variability. We studied 35 male (23) and female (12) human islet batches covering a range of donor ages and BMI. Islets were kept intact or dispersed into single cells and cultured in the presence of harmine, glucose, or heparin-binding epidermal growth factor-like growth factor (HB-EGF), and subsequently analyzed by immunohistochemistry or flow cytometry. Proliferating cells were identified by double labeling with EdU and Ki67 and glucagon, c-peptide or Nkx6.1, and cytokeratin-19 to respectively label alpha, beta, and ductal cells. Harmine and HB-EGF stimulated human beta-cell proliferation, but the effect of glucose was dependent on the assay and the donor. Harmine potently stimulated alpha-cell proliferation and both harmine and HB-EGF increased proliferation of insulin- and glucagon-negative cells, including cytokeratin 19-positive cells. Given the abundance of non-beta cells in human islet preparations, our results suggest that assessment of beta-cell mitogens requires complementary approaches and rigorous identification of cell identity using multiple markers. Nature Publishing Group UK 2021-05-28 /pmc/articles/PMC8163757/ /pubmed/34050242 http://dx.doi.org/10.1038/s41598-021-90643-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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/) . |
spellingShingle | Article Maachi, Hasna Ghislain, Julien Tremblay, Caroline Poitout, Vincent Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans |
title | Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans |
title_full | Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans |
title_fullStr | Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans |
title_full_unstemmed | Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans |
title_short | Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans |
title_sort | pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of langerhans |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163757/ https://www.ncbi.nlm.nih.gov/pubmed/34050242 http://dx.doi.org/10.1038/s41598-021-90643-3 |
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