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Every islet matters: improving the impact of human islet research

Abstract

Detailed characterization of human pancreatic islets is key to elucidating the pathophysiology of all forms of diabetes, especially type 2 diabetes. However, access to human pancreatic islets is limited. Pancreatic tissue for islet retrieval can be obtained from brain-dead organ donors or from individuals undergoing pancreatectomy, often referred to as ‘living donors’. Different protocols for human islet procurement can substantially impact islet function. This variability, coupled with heterogeneity between individuals and islets, results in analytical challenges to separate genuine disease pathology or differences between human donors from experimental noise. There are currently no international guidelines for human donor phenotyping, islet procurement and functional characterization. This lack of standardization means that substantial investments from multiple international efforts towards improved understanding of diabetes pathology cannot be fully leveraged. In this Perspective, we overview the status of the field of human islet research, highlight the challenges and propose actions that could accelerate research progress and increase understanding of type 2 diabetes to slow its pandemic spreading.

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Fig. 1: Comparative analysis of living and organ donors as the source of pancreatic tissue for islet studies.
Fig. 2: Models for recruitment of donors and pancreatic tissue for islet isolation and characterization.
Fig. 3: Models for islet isolation and characterization.
Fig. 4

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Acknowledgements

We are grateful to all islet donors and their families for their support in this endeavour. We thank F. J. Moller for helping with figure preparation. A.L.G. is a Wellcome Senior Fellow in Basic Biomedical Science. A.L.G. is funded by Wellcome (200837) and NIDDK (U01-DK105535, U01-DK085545, UM1DK126185, U01DK123743 and U24DK098085) and the Stanford Diabetes Research Center (NIDDK award P30DK116074). P.M. is supported by the Italian Ministry of University and Research, PRIN 2017, Molecular and Pathophysiological Heterogeneity of Autoimmune Diabetes: Implication for Precision Medicine, 2017KAM2R5_005. A.C.P. is funded by the HIRN (RRID: SCR_014393), the Human Pancreas Analysis Program (RRID: SCR_016202), DK106755, DK123716, DK112232, DK112217 and DK20593 (Vanderbilt Diabetes Research and Training Center), The Leona M. and Harry B. Helmsley Charitable Trust, and the Department of Veterans Affairs (BX000666). P.R. is funded by the Medical Research Council, the Swedish Research Council and The Leona M. and Harry B. Helmsley Charitable Trust. M. Sander is supported by grants from the National Institutes of Health (R01DK078803, R01DK068471, R01DK114427, R01DK122607, U01DK120429, U01HG012059 and UH3DK122639). M. Solimena is funded by the BMBF-German Center for Diabetes Research (DZD e.V.), the Deutsche Forschungsgemeinschaft (DFG; grants SO 818/10-1 and IRTG2251) and the DFG-ANR programme (SO 818/6-1). This work is also supported with funds by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 115881 (RHAPSODY) to M. Solimena, P.M. and M.I., and no. 115797 (INNODIA) and no. 945268 (INNODIA HARVEST) to M. Solimena and P.M. This Joint Undertaking receives support from the EU Horizon 2020 research and innovation programme, EFPIA, JDRF and The Leona M. and Harry B. Helmsley Charitable Trust. This work is further supported by the Swiss State Secretariat for Education‚ Research and Innovation under contract number 16.0097-2. The opinions expressed and arguments used herein do not necessarily reflect the official views of these funding bodies.

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All authors contributed to the planning and writing of the article and the conception of the figures.

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Correspondence to Anna L. Gloyn or Michele Solimena.

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A.L.G. and A.C.P. are members of the HPAP. A.L.G. is a member of the IIDP. A.L.G. and P.M are members of the Horizon 2020-funded T2DSystems. A.L.G., A.C.P. and M. Sander are members of the HIRN. P.M., M.I. and M. Solimena are members of RHAPSODY and IMIDIA; P.M. and M.I. are members of INNODIA. Through their membership of these consortia, the authors have received financial support as outlined in the acknowledgements.

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Nature Metabolism thanks Miriam Cnop, Michael Stitzel and the other, anonymous, reviewer for their contribution to the peer review of this work. Primary Handling Editor: Christoph Schmitt, in collaboration with the Nature Metabolism team.

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Gloyn, A.L., Ibberson, M., Marchetti, P. et al. Every islet matters: improving the impact of human islet research. Nat Metab 4, 970–977 (2022). https://doi.org/10.1038/s42255-022-00607-8

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