2025 GIGA Annual Report | 23 THE ISLET TISSUE PLASMINOGEN ACTIVATOR/PLASMIN SYSTEM IS UPREGULATED WITH HUMAN ISLET AMYLOID POLYPEPTIDE AGGREGATION AND PROTECTS BETA CELLS FROM AGGREGATION-INDUCED TOXICITY Esser N, Hogan MF, Templin AT, Akter R, Fountaine BS, Castillo JJ, El-Osta A, Manathunga L, Zhyvoloup A, Raleigh DP, Zraika S, Hull RL, Kahn SE. Islet amyloid deposition and reduced beta-cell mass are pathological hallmarks of type 2 diabetes. Aggregation of human islet amyloid polypeptide (hIAPP), the main peptide component of islet amyloid deposits in humans, is toxic to beta cells. A study led by Nathalie Esser from the Laboratory of Immunometabolism & Nutrition delineated a new role for the fibrinolytic system in modulating islet amyloidogenesis. Results showed a local tissue plasminogen activator (tPA)/plasmin system is specifically upregulated in vitro in amyloid-laden hIAPP transgenic mouse and human islets from donors with type 2 diabetes. Results also demonstrated that plasmin is an hIAPP-degrading enzyme that protects beta cells from hIAPP-induced toxicity. The study concluded that the tPA/ plasmin system could serve a protective function to limit islet amyloid deposition and its cytotoxic effects, suggesting that increasing tPA/plasmin activity could help prevent beta cell loss in type 2 diabetes. Diabetologia. 2024 Sep;67(9):1897-1911. doi: 10.1007/s00125-024-06161-0. p LINKS | Publication on ORBI | Nathalie Esser
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