@article{57059f9c9aa3445d82e38c91a192afb4,
title = "Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes",
abstract = "While cytoplasmic ARC maintains survival of insulin-producing pancreatic β cells, McKimpson et al. show that a pool of ARC relocates to the nucleus during diabetes where it paradoxically triggers cell death. The mechanism involves downregulation of AAT expression and secretion unleashing elastase-dependent loss of β cell adhesion and cell death.",
keywords = "ARC, alpha-1 antitrypsin, cell death, diabetes, serpins",
author = "McKimpson, {Wendy M.} and Yun Chen and Irving, {James A.} and Min Zheng and Jeremy Weinberger and Tan, {Wilson Lek Wen} and Zenia Tiang and Jagger, {Alistair M.} and Chua, {Streamson C.} and Pessin, {Jeffrey E.} and Foo, {Roger S.Y.} and Lomas, {David A.} and Kitsis, {Richard N.}",
note = "Funding Information: We acknowledge E. Miranda of “Sapienza” University of Rome, Italy and J. Perez of University of Malaga, Spain for generation of the human AAT antibody. This work was supported by grants from the NIH : R01HL60665 to R.N.K., P30DK020541 to J.E.P. supporting a pilot project to R.N.K., P30CA013330 (core facilities), T32GM007491 (predoctoral fellowship) to W.M.M., and 1K01DK121873 to W.M.M.; Medical Research Council (UK) N024842/1 , Alpha-1 Awareness, and the UCLH NIHR Biomedical Research Centre to D.A.L. and J.A.I.; Engineering and Physical Sciences Research Council /GlaxoSmithKline CASE Studentship to A.M.J.; and National Medical Research Council (NMRC) and Agency for Science, Technology and Research (A ∗ STAR), Singapore to R.S.-Y.F. This research was performed with the support of the Network for Pancreatic Organ Donors with Diabetes (nPOD), a collaborative type 1 diabetes research project sponsored by JDRF . Organ Procurement Organizations (OPO) partnering with nPOD to provide research resources are listed at http://www.jdrfnpod.org/for-partners/npod-partners/ . R.N.K. is supported by the Dr. Gerald and Myra Dorris Chair in Cardiovascular Disease . D.A.L. is an NIHR Senior Investigator. We thank the generosity of the Wilf Family for their support of this work. Graphical abstract was created with Biorender.com . Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = mar,
day = "22",
doi = "10.1016/j.devcel.2021.02.011",
language = "English (US)",
volume = "56",
pages = "747--760.e6",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "6",
}
