SerpinB13 antibodies promote β cell development and resistance to type 1 diabetes

Yury Kryvalap, Matthew L. Jiang, Nadzeya Kryvalap, Cole Hendrickson, Jan Czyzyk

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Pancreatic endocrine cell development is dependent on the rescue of the neurogenin3 (Ngn3) transcription factor from repression by Notch. The signals that prevent Notch signaling, thereby allowing the formation of pancreatic endocrine cells, remain unclear. We show that inhibiting serpinB13, a cathepsin L (CatL) protease inhibitor expressed in the pancreatic epithelium, caused in vitro and in vivo cleavage of the extracellular domain of Notch1. This was followed by a twofold increase in the Ngn3+ progenitor cell population and enhanced conversion of these cells to express insulin. Conversely, both recombinant serpinB13 protein and CatL deficiency down-regulated pancreatic Ngn3+ cell output. Mouse embryonic exposure to inhibitory anti-serpinB13 antibody resulted in increased islet cell mass and improved outcomes in streptozotocin-induced diabetes at 8 weeks of age. Moreover, anti-serpinB13 autoantibodies stimulated Ngn3+ endocrine progenitor formation in the pancreas and were associated with delayed progression to type 1 diabetes (T1D) in children. These data demonstrate long-Term impact of serpinB13 activity on islet biology and suggest that promoting protease activity by blocking this serpin may have prophylactic potential in T1D.

Original languageEnglish (US)
Article numberabf1587
JournalScience Translational Medicine
Issue number588
StatePublished - Apr 7 2021

Bibliographical note

Publisher Copyright:
© 2021 American Association for the Advancement of Science. All rights reserved.


  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Differentiation
  • Diabetes Mellitus, Type 1
  • Islets of Langerhans
  • Mice
  • Nerve Tissue Proteins

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article


Dive into the research topics of 'SerpinB13 antibodies promote β cell development and resistance to type 1 diabetes'. Together they form a unique fingerprint.

Cite this