Jian Ma, Bowen Xing, Yan Cao, Xin He, Kate E Bennett, Chao Tong, Chiying An, Taylor Hojnacki, Zijie Feng, Sunbin Deng, Sunbin Ling, Gengchen Xie, Yuan Wu, Yue Ren, Ming Yu, Bryson W Katona, Hongzhe Li, Ali Naji, Xianxin Hua
Pancreatic beta cells undergo compensatory proliferation in the early phase of type 2 diabetes. While pathways such as FoxM1 are involved in regulating compensatory beta cell proliferation, given the lack of therapeutics effectively targeting beta cell proliferation, other targetable pathways need to be identified. Herein, we show that Pbk, a serine/threonine protein kinase, is essential for high fat diet (HFD)-induced beta cell proliferation in vivo using a Pbk kinase deficiency knock-in mouse model. Mechanistically, JunD recruits menin and HDAC3 complex to the Pbk promoter to reduce histone H3 acetylation, leading to epigenetic repression of Pbk expression...
May 7, 2021: EMBO Molecular Medicine