PMID- 30066931 OWN - NLM STAT- MEDLINE DCOM- 20181108 LR - 20190816 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 18 IP - 3 DP - 2018 Sep TI - NSD2 is downregulated in T2DM and promotes beta cell proliferation and insulin secretion through the transcriptionally regulation of PDX1. PG - 3513-3520 LID - 10.3892/mmr.2018.9338 [doi] AB - Diabetes has become a major public health issue in the world. Type 2 diabetes mellitus (T2DM), also known as non‑insulin‑dependent 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 CCK‑8 assay and colony formation assay, revealed that NSD2 promoted the proliferation of pancreatic beta 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. FAU - Shi, Suqin AU - Shi S AD - Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. FAU - Zhao, Lu AU - Zhao L AD - Department of Endocrinology, The Third Affiliated Hospital of Henan University of TCM, Zhengzhou, Henan 450004, P.R. China. FAU - Zheng, Lili AU - Zheng L AD - Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. LA - eng PT - Journal Article DEP - 20180731 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Histones) RN - 0 (Homeodomain Proteins) RN - 0 (Insulin) RN - 0 (Repressor Proteins) RN - 0 (Trans-Activators) RN - 0 (pancreatic and duodenal homeobox 1 protein) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) RN - EC 2.1.1.43 (NSD2 protein, human) SB - IM MH - Adult MH - Cell Line MH - Cell Proliferation MH - Cell Survival MH - Diabetes Mellitus, Type 2/*genetics/*metabolism MH - Female MH - *Gene Expression Regulation MH - Histone-Lysine N-Methyltransferase/*genetics/metabolism MH - Histones/metabolism MH - Homeodomain Proteins/*genetics/metabolism MH - Humans MH - Insulin/*metabolism MH - Insulin Secretion MH - Insulin-Secreting Cells/*metabolism MH - Male MH - Methylation MH - Middle Aged MH - Repressor Proteins/*genetics/metabolism MH - Trans-Activators/*genetics/metabolism MH - Transcription, Genetic MH - Young Adult EDAT- 2018/08/02 06:00 MHDA- 2018/11/09 06:00 CRDT- 2018/08/02 06:00 PHST- 2018/02/10 00:00 [received] PHST- 2018/06/27 00:00 [accepted] PHST- 2018/08/02 06:00 [pubmed] PHST- 2018/11/09 06:00 [medline] PHST- 2018/08/02 06:00 [entrez] AID - 10.3892/mmr.2018.9338 [doi] PST - ppublish SO - Mol Med Rep. 2018 Sep;18(3):3513-3520. doi: 10.3892/mmr.2018.9338. Epub 2018 Jul 31.