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  Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes

Wigger, L., Barovic, M., Brunner, A.-D., Marzetta, F., Schoeniger, E., Mehl, F., et al. (2021). Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes. Nature Metabolism, 3(7), 1017-1031. doi:10.1038/s42255-021-00420-9.

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https://rdcu.be/cEUvK (Publisher version)
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 Creators:
Wigger, Leonore1, Author
Barovic, Marko1, Author
Brunner, Andreas-David2, Author              
Marzetta, Flavia1, Author
Schoeniger, Eyke1, Author
Mehl, Florence1, Author
Kipke, Nicole1, Author
Friedland, Daniela1, Author
Burdet, Frederic1, Author
Kessler, Camille1, Author
Lesche, Mathias1, Author
Thorens, Bernard1, Author
Bonifacio, Ezio1, Author
Legido-Quigley, Cristina1, Author
Barbier Saint Hilaire, Pierre1, Author
Delerive, Philippe1, Author
Dahl, Andreas1, Author
Klose, Christian1, Author
Gerl, Mathias J.1, Author
Simons, Kai1, Author
Aust, Daniela1, AuthorWeitz, Jurgen1, AuthorDistler, Marius1, AuthorSchulte, Anke M.1, AuthorMann, Matthias2, Author              Ibberson, Mark1, AuthorSolimena, Michele1, Author more..
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: PANCREATECTOMIZED PATIENTS; INSULIN-SECRETION; QUALITY-CONTROL; HIGH-THROUGHPUT; ORGAN DONORS; COPY-NUMBER; EXPRESSION; DEDIFFERENTIATION; IDENTIFICATION; NORMALIZATIONEndocrinology & Metabolism;
 Abstract: Wigger, Barovic and Brunner et al. perform a multidimensional analysis of islets from metabolically characterized patients who had undergone pancreatectomy, observing remarkable heterogeneity between samples from individuals with type 2 diabetes, thus arguing against models of linear beta-cell dedifferentiation in diabetes. Most research on human pancreatic islets is conducted on samples obtained from normoglycaemic or diseased brain-dead donors and thus cannot accurately describe the molecular changes of pancreatic islet beta cells as they progress towards a state of deficient insulin secretion in type 2 diabetes (T2D). Here, we conduct a comprehensive multi-omics analysis of pancreatic islets obtained from metabolically profiled pancreatectomized living human donors stratified along the glycemic continuum, from normoglycemia to T2D. We find that islet pools isolated from surgical samples by laser-capture microdissection display remarkably more heterogeneous transcriptomic and proteomic profiles in patients with diabetes than in non-diabetic controls. The differential regulation of islet gene expression is already observed in prediabetic individuals with impaired glucose tolerance. Our findings demonstrate a progressive, but disharmonic, remodelling of mature beta cells, challenging current hypotheses of linear trajectories toward precursor or transdifferentiation stages in T2D. Furthermore, through integration of islet transcriptomics with preoperative blood plasma lipidomics, we define the relative importance of gene coexpression modules and lipids that are positively or negatively associated with HbA1c levels, pointing to potential prognostic markers.

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Language(s): eng - English
 Dates: 2021-06-282021-07
 Publication Status: Published in print
 Pages: 23
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Nature Metabolism
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 3 (7) Sequence Number: - Start / End Page: 1017 - 1031 Identifier: ISSN: 2522-5812
CoNE: https://pure.mpg.de/cone/journals/resource/2522-5812