Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans

Abstract 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...

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Autores principales:	Hasna Maachi, Julien Ghislain, Caroline Tremblay, Vincent Poitout
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0c5672ccf4384164a7461795c4eafad4
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spelling	oai:doaj.org-article:0c5672ccf4384164a7461795c4eafad42021-12-02T15:49:53ZPronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans10.1038/s41598-021-90643-32045-2322https://doaj.org/article/0c5672ccf4384164a7461795c4eafad42021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90643-3https://doaj.org/toc/2045-2322Abstract 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.Hasna MaachiJulien GhislainCaroline TremblayVincent PoitoutNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hasna Maachi Julien Ghislain Caroline Tremblay Vincent Poitout Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans
description	Abstract 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	article
author	Hasna Maachi Julien Ghislain Caroline Tremblay Vincent Poitout
author_facet	Hasna Maachi Julien Ghislain Caroline Tremblay Vincent Poitout
author_sort	Hasna Maachi
title	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_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_sort	pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of langerhans
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0c5672ccf4384164a7461795c4eafad4
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Pronounced proliferation of non-beta cells in response to beta-cell mitogens in isolated human islets of Langerhans

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