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Title

The Role of Inflammation in β-cell Dedifferentiation

Authors
Nordmann, Thierry M
Dror, Erez
Schulze, Friederike
Traub, Shuyang
Böni-Schnetzler, Marianne
Donath, Marc Y
Published in Scientific reports. 2017, vol. 7, no. 1, 6285
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.
Keywords AnimalsAnti-Inflammatory Agents/pharmacologyCell DedifferentiationCells, CulturedCytokines/metabolismDiabetes Mellitus, Experimental/drug therapy/etiology/pathologyDiabetes Mellitus, Type 2/drug therapy/etiology/pathologyHumansInflammation/complications/physiopathologyInsulin/metabolismInsulin-Secreting Cells/drug effects/metabolism/pathologyMaleMiceMice, Inbred C57BL
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PMID: 28740254
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Other version: https://www.nature.com/articles/s41598-017-06731-w
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Research groups Création de tissus par bio-ingénieurie et régénération d'organes (1021)
La transplantation d'îlots de Langerhans (623)
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NORDMANN, Thierry M et al. The Role of Inflammation in β-cell Dedifferentiation. In: Scientific Reports, 2017, vol. 7, n° 1, p. 6285. doi: 10.1038/s41598-017-06731-w https://archive-ouverte.unige.ch/unige:138361

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Deposited on : 2020-07-10

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