The Role of Inflammation in β-cell Dedifferentiation

Abstract Chronic inflammation impairs insulin secretion and sensitivity. β-cell dedifferentiation has recently been proposed as a mechanism underlying β-cell failure in T2D. Yet the effect of inflammation on β-cell identity in T2D has not been studied. Therefore, we investigated whether pro-inflamma...

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Autores principales:	Thierry M. Nordmann, Erez Dror, Friederike Schulze, Shuyang Traub, Ekaterine Berishvili, Charlotte Barbieux, Marianne Böni-Schnetzler, Marc Y. Donath
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6f906ade44424de0a8b12cce0ea33f04
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spelling	oai:doaj.org-article:6f906ade44424de0a8b12cce0ea33f042021-12-02T15:06:12ZThe Role of Inflammation in β-cell Dedifferentiation10.1038/s41598-017-06731-w2045-2322https://doaj.org/article/6f906ade44424de0a8b12cce0ea33f042017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06731-whttps://doaj.org/toc/2045-2322Abstract Chronic inflammation impairs insulin secretion and sensitivity. β-cell dedifferentiation has recently been proposed as a mechanism underlying β-cell failure in T2D. Yet the effect of inflammation on β-cell identity in T2D has not been studied. Therefore, we investigated whether pro-inflammatory cytokines induce β-cell dedifferentiation and whether anti-inflammatory treatments improve insulin secretion via β-cell redifferentiation. We observed that IL-1β, IL-6 and TNFα promote β-cell dedifferentiation in cultured human and mouse islets, with IL-1β being the most potent one of them. In particular, β-cell identity maintaining transcription factor Foxo1 was downregulated upon IL-1β exposure. In vivo, anti-IL-1β, anti-TNFα or NF-kB inhibiting sodium salicylate treatment improved insulin secretion of isolated islets. However, only TNFα antagonism partially prevented the loss of β-cell identity gene expression. Finally, the combination of IL-1β and TNFα antagonism improved insulin secretion of ex vivo isolated islets in a synergistic manner. Thus, while inflammation triggered β-cell dedifferentiation and dysfunction in vitro, this mechanism seems to be only partly responsible for the observed in vivo improvements in insulin secretion.Thierry M. NordmannErez DrorFriederike SchulzeShuyang TraubEkaterine BerishviliCharlotte BarbieuxMarianne Böni-SchnetzlerMarc Y. DonathNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Thierry M. Nordmann Erez Dror Friederike Schulze Shuyang Traub Ekaterine Berishvili Charlotte Barbieux Marianne Böni-Schnetzler Marc Y. Donath The Role of Inflammation in β-cell Dedifferentiation
description	Abstract Chronic inflammation impairs insulin secretion and sensitivity. β-cell dedifferentiation has recently been proposed as a mechanism underlying β-cell failure in T2D. Yet the effect of inflammation on β-cell identity in T2D has not been studied. Therefore, we investigated whether pro-inflammatory cytokines induce β-cell dedifferentiation and whether anti-inflammatory treatments improve insulin secretion via β-cell redifferentiation. We observed that IL-1β, IL-6 and TNFα promote β-cell dedifferentiation in cultured human and mouse islets, with IL-1β being the most potent one of them. In particular, β-cell identity maintaining transcription factor Foxo1 was downregulated upon IL-1β exposure. In vivo, anti-IL-1β, anti-TNFα or NF-kB inhibiting sodium salicylate treatment improved insulin secretion of isolated islets. However, only TNFα antagonism partially prevented the loss of β-cell identity gene expression. Finally, the combination of IL-1β and TNFα antagonism improved insulin secretion of ex vivo isolated islets in a synergistic manner. Thus, while inflammation triggered β-cell dedifferentiation and dysfunction in vitro, this mechanism seems to be only partly responsible for the observed in vivo improvements in insulin secretion.
format	article
author	Thierry M. Nordmann Erez Dror Friederike Schulze Shuyang Traub Ekaterine Berishvili Charlotte Barbieux Marianne Böni-Schnetzler Marc Y. Donath
author_facet	Thierry M. Nordmann Erez Dror Friederike Schulze Shuyang Traub Ekaterine Berishvili Charlotte Barbieux Marianne Böni-Schnetzler Marc Y. Donath
author_sort	Thierry M. Nordmann
title	The Role of Inflammation in β-cell Dedifferentiation
title_short	The Role of Inflammation in β-cell Dedifferentiation
title_full	The Role of Inflammation in β-cell Dedifferentiation
title_fullStr	The Role of Inflammation in β-cell Dedifferentiation
title_full_unstemmed	The Role of Inflammation in β-cell Dedifferentiation
title_sort	role of inflammation in β-cell dedifferentiation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6f906ade44424de0a8b12cce0ea33f04
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The Role of Inflammation in β-cell Dedifferentiation

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