The role of proteases and serpin protease inhibitors in β-cell biology and diabetes

Research output: Contribution to journalReview articlepeer-review

Abstract

Regulation of the equilibrium between proteases and their inhibitors is fundamental to health maintenance. Consequently, developing a means of targeting protease activity to promote tissue regeneration and inhibit inflammation may offer a new strategy in therapy development for diabetes and other diseases. Specifically, recent efforts have focused on serine protease inhibitors, known as serpins, as potential therapeutic targets. The serpin protein family comprises a broad range of protease inhibitors, which are categorized into 16 clades that are all extracellular, with the exception of Clade B, which controls mostly intracellular proteases, including both serine-and pa-pain-like cysteine proteases. This review discusses the most salient, and sometimes opposing, views that either inhibition or augmentation of protease activity can bring about positive outcomes in pancreatic islet biology and inflammation. These potential discrepancies can be reconciled at the molecular level as specific proteases and serpins regulate distinct signaling pathways, thereby playing equally distinct roles in health and disease development.

Original languageEnglish (US)
Article number67
JournalBiomolecules
Volume12
Issue number1
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
Funding: Some of the work described in the manuscript was supported by grants from the Juvenile Diabetes Research Foundation (grant #17-2013-428), the American Diabetes Association (grant# 1-17-ICTS-083) and the National Institutes of Health (grant #DK108739-01A1).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Diabetes
  • Pancreatic islet
  • Protease
  • Serpin

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

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