The Role Of NIK In Islet ? Cells And Its Mechanism

Diabetes is a metabolic disease caused by the interaction of genetic and environmental factors.Its pathogenesis is mainly due to inadequate secretion of insulin absolute(?diabetes)or relative secretes inadequacy(? diabetes),and the decreased sensitivity of target cells to insulin causes a series of metabolic disorders including sugar,fat and protein.In the body,there are two main hormones that regulate the balance of blood sugar.One is the glucagon produced by islet ? cells.During hypoglycemia,glucagon speeds up glucone ogen-esis,reducing glucose metabolism and increasing glucose synthesis.The other is insulin,which is pro-duced by islet ? cells.During hyperglycemia,insulin accelerates glycolysis and promotes glycogen synthesis and storage.At the same time,the inhibition of glycogen decomposition and heterogenesis increases the utilization of blood glucose and decreases the source of blood glucose.Studies have shown that the non-classical NF-?B signaling is involved in islet? cells damage.NF-?B inducing kinase(NIK)plays an important role as a key molecule in the NF-?B2 signaling pathway.However,the mechanism of its action in cells is unclear.The purpose of this study was to investigate the effect of NIK on the growth and function of islet cells and the mechanism of action.The study overexpressed the NIK adenovirus in the islet ? cellline Ins-1 832/13.The effects of NIK on Ins-1 832/13 cells were determined by ELISA,MTT,RNA-seq and q PCR.It was shown that overexpression of NIK could induce apoptosis and decrease the number of islet ? cells.It also reduces insulin synthesis and secretion and results in impaired insulin function.At the m RNA level,overexpression NIK causes a series of lesions in islet ? cells by up-regulating the expression of related inflammatory genes,MHC genes,and the expression of insulin synthesis and secretion genes.And NIK's small molecule inhibitor — B022,significantly protects NIK induced damage.At the same time,B022 also has a good inhibitory effect on Ins-1 832/13 damage caused by H2O2-induced oxidative stress.The study provides an important reference for the in vivo study of the mechanism of NIK in islet ? cells,and also reveals the role of NF-?B2 signaling pathway in islet ? cells and its mechanism.Moreover,we found that B022 can effectively inhibit NIK,which provides new possibilities for the research of clinical drugs for inflammatory diseases targeting NIK.