Cell Death and Disease (May 2022)

NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes

  • Peng Xiao,
  • Tatiana Takiishi,
  • Natalia Moretti Violato,
  • Giada Licata,
  • Francesco Dotta,
  • Guido Sebastiani,
  • Lorella Marselli,
  • Sumeet Pal Singh,
  • Mozes Sze,
  • Geert Van Loo,
  • Emmanuel Dejardin,
  • Esteban Nicolas Gurzov,
  • Alessandra Kupper Cardozo

DOI
https://doi.org/10.1038/s41419-022-04931-5
Journal volume & issue
Vol. 13, no. 5
pp. 1 – 11

Abstract

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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.