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Schepp, F.* ; Schubert, U. ; Schmid, J. ; Lehmann, S. ; Latunde-Dada, G.O.* ; Kose, T.* ; Steenblock, C.* ; Bornstein, S.R. ; Linkermann, A.* ; Ludwig, B.

Mechanistic insights into ferroptotic cell death in pancreatic islets.

Horm. Metab. Res., DOI: 10.1055/a-2190-2803 (2023)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Ferroptosis was recently identified as a non-apoptotic, iron-dependent cell death mechanism that is involved in various pathologic conditions. There is first evidence for its significance also in the context of islet isolation and transplantation. Transplantation of pancreatic human islets is a viable treatment strategy for patients with complicated diabetes mellitus type 1 (T1D) that suffer from severe hypoglycemia. A major determinant for functional outcome is the initial islet mass transplanted. Efficient islet isolation procedures and measures to minimize islet loss are therefore of high relevance. To this end, better understanding and subsequent targeted inhibition of cell death during islet isolation and transplantation is an effective approach. In this study, we aimed to elucidate the mechanism of ferroptosis in pancreatic islets. Using a rodent model, isolated islets were characterized relating to the effects of experimental induction (RSL3) and inhibition (Fer1) of ferroptotic pathways. Besides viability, survival, and function, the study focused on characteristic ferroptosis-associated intracellular changes such as MDA level, iron concentration and the expression of ACSL4. The study demonstrates that pharmaceutical induction of ferroptosis by RSL3 causes enhancement of oxidative stress and leads to an increase of intracellular iron, zinc and MDA concentration, as well as the expression of ACSL4 protein. Consequently, a massive reduction of islet function, viability, and survival was found. Fer1 has the potential to inhibit and attenuate these cellular changes and thereby protect the islets from cell death.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cell Death ; Diabetes ; Ferroptosis ; Insulin Secretion ; Iron ; Islets ; Ros
ISSN (print) / ISBN 0018-5043
e-ISSN 1439-4286
Journal Hormone and Metabolic Research
Publisher Thieme
Publishing Place Rudigerstr 14, D-70469 Stuttgart, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)
Grants Deutsche Forschungsgemeinschaft