NSD2 is downregulated in T2DM and promotes ß cell proliferation and insulin secretion through the transcriptionally regulation of PDX1.

ABSTRACT

Diabetes has become a major public health issue in the world. Type 2 diabetes mellitus (T2DM), also known as non­insulin­dependent diabetes mellitus, has been identified to result in an inability to compensate for insulin resistance. A previous study has shown that NSD2 regulates glucose metabolism; however, whether NSD2 serves roles in diabetes has not been thoroughly elucidated to date. In present study, the expression of NSD2 in blood samples from patients with T2DM was compared with that in healthy volunteers. Notably, the expression of NSD2 was negatively correlated with glucose concentration but positively associated with PDX1 expression. Several functional experiments, including CCK­8 assay and colony formation assay, revealed that NSD2 promoted the proliferation of pancreatic ß cell lines. Moreover, ectopic expression of NSD2 significantly promoted insulin secretion. In addition, NSD2 served as a transfection factor and it was identified that NSD2 transcriptionally regulated PDX1 expression through its H3K36me2 methyltransferase activity. The present study indicated that NSD2 may be a novel molecular therapy target of T2DM.