The transcription factor nuclear factor-kappa B (NF-kappa B) has a key role in the pathogenesis of diabetes and its complications. Although activation of the canonical NF-kappa B pathway in beta-cells is generally deleterious, little is known about the role of the non-canonical NF-kappa B signalling and its main regulator, the NF-kappa B-inducing kinase (NIK), on pancreatic beta-cell survival and function. Previous studies based on models of NIK overexpression in pancreatic islet cells showed that NIK induced either spontaneous beta-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 beta-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 beta-cell survival, function, and downstream gene regulation. Taken together, our data suggest that NIK activation is dispensable for the development of diabetes.

Xiao, P., Takiishi, T., Violato, N.M., Licata, G., Dotta, F., Sebastiani, G., et al. (2022). NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes. CELL DEATH & DISEASE, 13(5), 1-11 [10.1038/s41419-022-04931-5].

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

Licata, Giada;Dotta, Francesco
Membro del Collaboration Group
;
Sebastiani, Guido
Membro del Collaboration Group
;
2022-01-01

Abstract

The transcription factor nuclear factor-kappa B (NF-kappa B) has a key role in the pathogenesis of diabetes and its complications. Although activation of the canonical NF-kappa B pathway in beta-cells is generally deleterious, little is known about the role of the non-canonical NF-kappa B signalling and its main regulator, the NF-kappa B-inducing kinase (NIK), on pancreatic beta-cell survival and function. Previous studies based on models of NIK overexpression in pancreatic islet cells showed that NIK induced either spontaneous beta-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 beta-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 beta-cell survival, function, and downstream gene regulation. Taken together, our data suggest that NIK activation is dispensable for the development of diabetes.
2022
Xiao, P., Takiishi, T., Violato, N.M., Licata, G., Dotta, F., Sebastiani, G., et al. (2022). NF-κB-inducing kinase (NIK) is activated in pancreatic β-cells but does not contribute to the development of diabetes. CELL DEATH & DISEASE, 13(5), 1-11 [10.1038/s41419-022-04931-5].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1211013