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Karampelias, C. ; Băloiu, B.* ; Rathkolb, B. ; da Silva Buttkus, P. ; Bachar-Wikström, E.* ; Marschall, S. ; Fuchs, H. ; Gailus-Durner, V. ; Chu, L.W.* ; Hrabě de Angelis, M. ; Andersson, O.*

Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.

Life Sci. All. 7:15 (2024)

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	Open Access Gold

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Regeneration of insulin-producing β-cells is an alternative avenue to manage diabetes, and it is crucial to unravel this process in vivo during physiological responses to the lack of β-cells. Here, we aimed to characterize how hepatocytes can contribute to β-cell regeneration, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of β-cell loss. Using lineage tracing, we show that hepatocytes do not directly convert into β-cells even under extreme β-cell ablation conditions. A transcriptomic analysis of isolated hepatocytes after β-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role of the molybdenum cofactor (Moco) biosynthetic pathway in β-cell regeneration and glucose metabolism in zebrafish. Consistently, molybdenum cofactor synthesis 2 (Mocs2) haploinsufficiency in mice indicated dysregulated glucose metabolism and liver function. Together, our study sheds light on the liver-pancreas crosstalk and suggests that the molybdenum cofactor biosynthesis pathway should be further studied in relation to glucose metabolism and diabetes.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Insulin-resistance; Endocrine Pancreas; Gene-expression; Immune-system; Ductal Cells; Alpha-cells; In-vivo; B-cells; Zebrafish; Progenitors

ISSN (print) / ISBN 2575-1077

e-ISSN 2575-1077

Journal Life Science Alliance

Quellenangaben Volume: 7, Issue: 11, Article Number: 15

Publisher EMBO Press

Publishing Place Heidelberg

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Regeneration Research (IDR)
Institute of Experimental Genetics (IEG)

Grants Uppsala Multidisciplinary Center for Advanced Computational Science
Novo Nordisk Foundation
Diabetes Wellness
Cancerfonden
Strategic Research Programmes in Diabetes at the Karolinska Institutet
Novo Nordisk A/S
German Federal Ministry of Education and Research Infrafrontier grant
German Center for Diabetes Research
Science for Life Laboratory
Knut and Alice Wallenberg Foundation
Swedish Research Council