美国哈佛干细胞研究所Rohit N. Kulkarni研究组发现，过量的胰腺弹性酶(PE)通过破坏机械信号和PAR2途径改变腺泡-β细胞的通讯。相关论文于2023年6月19日发表在《细胞—代谢》杂志上。
他们报道PE在2型糖尿病(T2D)患者的腺泡细胞和胰岛中上调，并对β细胞活力产生负面影响。通过高通量筛选试验，他们发现telaprevir是一种有效的PE抑制剂，可以提高人类和啮齿动物体内和体外的β细胞活力，并改善胰岛素抵抗小鼠的葡萄糖耐量。磷酸化抗体微阵列和单细胞RNA测序分析发现，PAR2和机械信号通路是PE的潜在介质。综上所述，他们的工作强调了PE作为腺泡-β细胞串扰的潜在调节剂，其作用是限制β细胞的活力，导致T2D。
据悉，1型(T1D)或T2D是由产生胰岛素的功能性β细胞缺陷引起的。因此，β细胞营养因子的鉴定可能有助于开发对抗糖尿病的治疗策略。SerpinB1(一种促进人类β细胞生长的弹性酶抑制剂)的发现促使他们假设PE调节β细胞的活力。
附：英文原文
Title: Excess pancreatic elastase alters acinar-β cell communication by impairing the mechano-signaling and the PAR2 pathways
Author: Giorgio Basile, Amedeo Vetere, Jiang Hu, Oluwaseun Ijaduola, Yi Zhang, Ka-Cheuk Liu, Amira M. Eltony, Dario F. De Jesus, Kazuki Fukuda, Grace Doherty, Colin A. Leech, Oleg G. Chepurny, George G. Holz, Seok-Hyun Yun, Olov Andersson, Amit Choudhary, Bridget K. Wagner, Rohit N. Kulkarni
Issue&Volume: 2023-06-19
Abstract: Type 1 (T1D) or type 2 diabetes (T2D) are caused by a deficit of functional insulin-producingβ cells. Thus, the identification of β cell trophic agents could allow the developmentof therapeutic strategies to counteract diabetes. The discovery of SerpinB1, an elastaseinhibitor that promotes human β cell growth, prompted us to hypothesize that pancreaticelastase (PE) regulates β cell viability. Here, we report that PE is up-regulatedin acinar cells and in islets from T2D patients, and negatively impacts β cell viability.Using high-throughput screening assays, we identified telaprevir as a potent PE inhibitorthat can increase human and rodent β cell viability in vitro and in vivo and improve glucose tolerance in insulin-resistant mice. Phospho-antibody microarraysand single-cell RNA sequencing analysis identified PAR2 and mechano-signaling pathwaysas potential mediators of PE. Taken together, our work highlights PE as a potentialregulator of acinar-β cell crosstalk that acts to limit β cell viability, leadingto T2D.
DOI: 10.1016/j.cmet.2023.05.007
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00184-5
Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx
本期文章：《细胞—代谢》：Online/在线发表
