NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes
In: Cell Death and Disease, Jg. 13 (2022), Heft 5, S. 1-11
Online
academicJournal
Zugriff:
Abstract The transcription factor nuclear factor-κB (NF-κB) has a key role in the pathogenesis of diabetes and its complications. Although activation of the canonical NF-κB pathway in β-cells is generally deleterious, little is known about the role of the non-canonical NF-κB signalling and its main regulator, the NF-κB-inducing kinase (NIK), on pancreatic β-cell survival and function. Previous studies based on models of NIK overexpression in pancreatic islet cells showed that NIK induced either spontaneous β-cell death due to islet inflammation or glucose intolerance during diet-induced obesity (DIO) in mice. Therefore, NIK has been proposed as a potential target for diabetes therapy. However, no clear studies showed whether inhibition of NIK improves diabetes development. Here we show that genetic silencing of NIK in pancreatic β-cells neither modifies diabetes incidence nor inflammatory responses in a mouse model of immune-mediated diabetes. Moreover, NIK silencing in DIO mice did not influence body weight gain, nor glucose metabolism. In vitro studies corroborated the in vivo findings in terms of β-cell survival, function, and downstream gene regulation. Taken together, our data suggest that NIK activation is dispensable for the development of diabetes.
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NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes
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Autor/in / Beteiligte Person: | Xiao, Peng ; Takiishi, Tatiana ; Natalia Moretti Violato ; Licata, Giada ; Dotta, Francesco ; Sebastiani, Guido ; Marselli, Lorella ; Sumeet Pal Singh ; Sze, Mozes ; Geert Van Loo ; Dejardin, Emmanuel ; Esteban Nicolas Gurzov ; Alessandra Kupper Cardozo |
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Zeitschrift: | Cell Death and Disease, Jg. 13 (2022), Heft 5, S. 1-11 |
Veröffentlichung: | Nature Publishing Group, 2022 |
Medientyp: | academicJournal |
ISSN: | 2041-4889 (print) |
DOI: | 10.1038/s41419-022-04931-5 |
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