The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity
The fibrinolytic system is upregulated in islets with hIAPP aggregation. Plasmin rapidly degrades hIAPP, limiting its aggregation into amyloid and thus protecting beta cells from hIAPP-induced toxicity. Thus, increasing islet plasmin activity might be a strategy to limit beta cell loss in type 2 diabetes.
Authors
- Joseph Castillo (ORCID: https://orcid.org/0000-0003-4080-2545)
- Andrew T. Templin (ORCID: https://orcid.org/0000-0002-6241-9304)
- Rebecca L. Hull (ORCID: https://orcid.org/0000-0001-9690-4087)
- Meghan F. Hogan (ORCID: https://orcid.org/0000-0002-5767-1599)
- Lakshan Manathunga (ORCID: https://orcid.org/0000-0002-9809-4193)
- Sakeneh Zraika (ORCID: https://orcid.org/0000-0003-4831-7034)
- Daniel P. Raleigh (ORCID: https://orcid.org/0000-0003-3248-7493)
- Alexander Zhyvoloup (ORCID: https://orcid.org/0000-0003-2450-8979)
- Brendy S Fountaine (ORCID: https://orcid.org/0000-0001-7936-471X)
- Nathalie Esser (ORCID: https://orcid.org/0000-0003-1823-3817)
- Steven E. Kahn (ORCID: https://orcid.org/0000-0001-7307-9002)
- Rehana Akter (ORCID: https://orcid.org/0000-0002-4475-3093)
- Assam El‐Osta (ORCID: https://orcid.org/0000-0001-7968-7375)
Institutions
- Baker Heart and Diabetes Institute (AU)
- University of Liège (BE)
- University of Washington (US)
- VA Puget Sound Health Care System (US)
- Richard L. Roudebush VA Medical Center (US)
- Centre Hospitalier Universitaire de Liège (BE)
- Institute of Structural and Molecular Biology (GB)
- Indiana University School of Medicine
- University College London (GB)
- Indiana University – Purdue University Indianapolis (US)
- Stony Brook University (US)
Publication Details
- Journal
- Diabetologia
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1007/s00125-024-06161-0
- Citations
- 3
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 1.72
Funders
- American Diabetes Association
- U.S. Department of Veterans Affairs
- Belgian American Educational Foundation
- University of Washington
- Wellcome Trust
- Juvenile Diabetes Research Foundation Australia
- Fonds De La Recherche Scientifique - FNRS
- Fonds Léon Fredericq
- European Association for the Study of Diabetes
- Société Francophone du Diabète
- Fonds Baillet Latour
- Stony Brook University
- National Institutes of Health
- Diabetes Research Center, University of Washington
- Medical Research Council
- National Health and Medical Research Council