Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells

Neonatal porcine islets-like clusters (NPICCs) are a promising source for cell therapy of type 1 diabetes. Freshly isolated NPICCs are composed of progenitor cells and endocrine cells, which undergo a maturation process lasting several weeks until the normal beta cell function has developed. Here, w...

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Autores principales:	Yichen Zhang, Yutian Lei, Mohsen Honarpisheh, Elisabeth Kemter, Eckhard Wolf, Jochen Seissler
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	islet development short chain fatty acids butyrate HDAC inhibitor porcine islets NPICCs Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/09918cbd73f843e9a9c24c7c4e0b8b74
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spelling	oai:doaj.org-article:09918cbd73f843e9a9c24c7c4e0b8b742021-11-25T17:13:17ZButyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells10.3390/cells101132492073-4409https://doaj.org/article/09918cbd73f843e9a9c24c7c4e0b8b742021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3249https://doaj.org/toc/2073-4409Neonatal porcine islets-like clusters (NPICCs) are a promising source for cell therapy of type 1 diabetes. Freshly isolated NPICCs are composed of progenitor cells and endocrine cells, which undergo a maturation process lasting several weeks until the normal beta cell function has developed. Here, we investigated the effects of short-chain fatty acids on the maturation of islet cells isolated from two to three day-old piglets. NPICCs were cultivated with acetate, butyrate and propionate (0–2000 µM) for one to eight days. Incubation with butyrate resulted in a significant upregulation of insulin gene expression and an increased beta cell number, whereas acetate or propionate had only marginal effects. Treatment with specific inhibitors of G-protein-coupled receptor GPR41 (β-hydroxybutyrate) and/or GPR43 (GPLG0974) did not abolish butyrate induced insulin expression. However, incubation of NPICCs with class I histone deacetylase inhibitors (HDACi) mocetinostat and MS275, but not selective class II HDACi (TMP269, MC1568) mimicked the butyrate effect on beta cell differentiation. Our study revealed that butyrate treatment has the capacity to increase the number of beta cells, which may be predominantly mediated through its HDAC inhibitory activity. Butyrate and specific class I HDAC inhibitors may represent beneficial supplements to promote differentiation of neonatal porcine islet cells towards beta cells for cell replacement therapies.Yichen ZhangYutian LeiMohsen HonarpishehElisabeth KemterEckhard WolfJochen SeisslerMDPI AGarticleislet developmentshort chain fatty acidsbutyrateHDAC inhibitorporcine isletsNPICCsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3249, p 3249 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	islet development short chain fatty acids butyrate HDAC inhibitor porcine islets NPICCs Biology (General) QH301-705.5
spellingShingle	islet development short chain fatty acids butyrate HDAC inhibitor porcine islets NPICCs Biology (General) QH301-705.5 Yichen Zhang Yutian Lei Mohsen Honarpisheh Elisabeth Kemter Eckhard Wolf Jochen Seissler Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells
description	Neonatal porcine islets-like clusters (NPICCs) are a promising source for cell therapy of type 1 diabetes. Freshly isolated NPICCs are composed of progenitor cells and endocrine cells, which undergo a maturation process lasting several weeks until the normal beta cell function has developed. Here, we investigated the effects of short-chain fatty acids on the maturation of islet cells isolated from two to three day-old piglets. NPICCs were cultivated with acetate, butyrate and propionate (0–2000 µM) for one to eight days. Incubation with butyrate resulted in a significant upregulation of insulin gene expression and an increased beta cell number, whereas acetate or propionate had only marginal effects. Treatment with specific inhibitors of G-protein-coupled receptor GPR41 (β-hydroxybutyrate) and/or GPR43 (GPLG0974) did not abolish butyrate induced insulin expression. However, incubation of NPICCs with class I histone deacetylase inhibitors (HDACi) mocetinostat and MS275, but not selective class II HDACi (TMP269, MC1568) mimicked the butyrate effect on beta cell differentiation. Our study revealed that butyrate treatment has the capacity to increase the number of beta cells, which may be predominantly mediated through its HDAC inhibitory activity. Butyrate and specific class I HDAC inhibitors may represent beneficial supplements to promote differentiation of neonatal porcine islet cells towards beta cells for cell replacement therapies.
format	article
author	Yichen Zhang Yutian Lei Mohsen Honarpisheh Elisabeth Kemter Eckhard Wolf Jochen Seissler
author_facet	Yichen Zhang Yutian Lei Mohsen Honarpisheh Elisabeth Kemter Eckhard Wolf Jochen Seissler
author_sort	Yichen Zhang
title	Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells
title_short	Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells
title_full	Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells
title_fullStr	Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells
title_full_unstemmed	Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells
title_sort	butyrate and class i histone deacetylase inhibitors promote differentiation of neonatal porcine islet cells into beta cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/09918cbd73f843e9a9c24c7c4e0b8b74
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_version_	1718412571698003968

Butyrate and Class I Histone Deacetylase Inhibitors Promote Differentiation of Neonatal Porcine Islet Cells into Beta Cells

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