Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.
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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, Hrabě de Angelis M, Andersson O
Life Sci. Alliance 7 (11) e202402771 [2024-11-00; online 2024-08-19]
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.
Bioinformatics Support for Computational Resources [Service]
NGI Stockholm (Genomics Production)
National Genomics Infrastructure
PubMed 39159974
DOI 10.26508/lsa.202402771
Crossref 10.26508/lsa.202402771
pmc: PMC11333758
pii: 7/11/e202402771