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Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro

As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell population. Both mou...

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Detalles Bibliográficos
Autores principales: Millette, Katelyn, Rodriguez, Keith, Sheng, Xia, Finley, Stacey D., Georgia, Senta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961548/
https://www.ncbi.nlm.nih.gov/pubmed/35204716
http://dx.doi.org/10.3390/biom12020215
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author Millette, Katelyn
Rodriguez, Keith
Sheng, Xia
Finley, Stacey D.
Georgia, Senta
author_facet Millette, Katelyn
Rodriguez, Keith
Sheng, Xia
Finley, Stacey D.
Georgia, Senta
author_sort Millette, Katelyn
collection PubMed
description As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell population. Both mouse and human studies have established that beta cell mass expansion occurs rapidly during pregnancy. To investigate the mechanisms of beta cell mass expansion during pregnancy, we developed a novel in vivo and in vitro models of pseudopregnancy. Our models demonstrate that pseudopregnancy promotes beta cell mass expansion in parous mice, and this expansion is driven by beta cell proliferation rather than hypertrophy. Importantly, estrogen, progesterone, and placental lactogen induce STAT5A signaling in the pseudopregnancy model, demonstrating that this model successfully recapitulates pregnancy-induced beta cell replication. We then created an in vitro model of pseudopregnancy and found that the combination of estrogen and placental lactogen induced beta cell replication in human islets and rat insulinoma cells. Therefore, beta cells both in vitro and in vivo increase proliferation when subjected to the pseudopregnancy cocktail compared to groups treated with estradiol or placental lactogen alone. The pseudopregnancy models described here may help inform novel methods of inducing beta cell replication in patients with diabetes.
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spelling pubmed-89615482022-03-30 Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro Millette, Katelyn Rodriguez, Keith Sheng, Xia Finley, Stacey D. Georgia, Senta Biomolecules Article As patients recently diagnosed with T1D and patients with T2D have residual beta cell mass, there is considerable effort in beta cell biology to understand the mechanisms that drive beta cell regeneration as a potential cellular therapy for expanding patients’ residual beta cell population. Both mouse and human studies have established that beta cell mass expansion occurs rapidly during pregnancy. To investigate the mechanisms of beta cell mass expansion during pregnancy, we developed a novel in vivo and in vitro models of pseudopregnancy. Our models demonstrate that pseudopregnancy promotes beta cell mass expansion in parous mice, and this expansion is driven by beta cell proliferation rather than hypertrophy. Importantly, estrogen, progesterone, and placental lactogen induce STAT5A signaling in the pseudopregnancy model, demonstrating that this model successfully recapitulates pregnancy-induced beta cell replication. We then created an in vitro model of pseudopregnancy and found that the combination of estrogen and placental lactogen induced beta cell replication in human islets and rat insulinoma cells. Therefore, beta cells both in vitro and in vivo increase proliferation when subjected to the pseudopregnancy cocktail compared to groups treated with estradiol or placental lactogen alone. The pseudopregnancy models described here may help inform novel methods of inducing beta cell replication in patients with diabetes. MDPI 2022-01-26 /pmc/articles/PMC8961548/ /pubmed/35204716 http://dx.doi.org/10.3390/biom12020215 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Millette, Katelyn
Rodriguez, Keith
Sheng, Xia
Finley, Stacey D.
Georgia, Senta
Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
title Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
title_full Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
title_fullStr Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
title_full_unstemmed Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
title_short Exogenous Lactogenic Signaling Stimulates Beta Cell Replication In Vivo and In Vitro
title_sort exogenous lactogenic signaling stimulates beta cell replication in vivo and in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961548/
https://www.ncbi.nlm.nih.gov/pubmed/35204716
http://dx.doi.org/10.3390/biom12020215
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