Islet α-cell Inflammation Induced By NF-κB inducing kinase (NIK) Leads to Hypoglycemia, Pancreatitis, Growth Retardation, and Postnatal Death in Mice

Abstract

Islet -cell dysfunction has been shown to contribute to type 2 diabetes; however, whether islet -cell inflammation is involved in the occurrence of pancreatitis is largely unknown. The aims of this study were to investigate how NF-B inducing kinase (NIK) regulates pancreatic -cell function, both in vitro and in vivo, and to assess how islet -cell inflammation induced by NIK affects the development of pancreatitis. Methods: We utilized adenovirus-mediated NIK overexpression, ELISA, qPCR, RNA-seq, and Western blot analyses to study the role of NIK in islet cells in vitro. Islet -cell-specific NIK overexpressing (-NIK-OE) mice were generated, and pancreatic /-cell function and the occurrence of pancreatitis in these mice were assessed via ELISA, qPCR, and immunohistochemical analyses.