Characterization of liver-pancreas crosstalk following beta-cell loss reveals a role for the molybdenum cofactor in beta-cell regeneration

Karampelias, C.; Baloiu, B.; Rathkolb, B.; da Silva-Buttkus, P.; Bachar-Wikstrom, E.; Marschall, S.; Fuchs, H.; Gailus-Durner, V.; Chu, L.; Hrabe de Angelis, M.; Andersson, O.

doi:10.1101/2024.04.09.588677

bioRxiv · 10.1101/2024.04.09.588677

Characterization of liver-pancreas crosstalk following beta-cell loss reveals a role for the molybdenum cofactor in beta-cell regeneration

Karampelias, C.·Baloiu, B.·Rathkolb, B.·da Silva-Buttkus, P.·Bachar-Wikstrom, E.·Marschall, S.·Fuchs, H.·Gailus-Durner, V.·Chu, L.·Hrabe de Angelis, M.·Andersson, O.

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Abstract

Regeneration of insulin-producing {beta}-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 {beta}-cells. Here, we aimed to characterize how hepatocytes can contribute to {beta}-cell regeneration in a zebrafish model of {beta}-cell ablation. Using lineage-tracing, we show that hepatocytes do not directly convert into {beta}-cells even under extreme {beta}-cell ablation conditions. A transcriptomics analysis of isolated hepatocytes following {beta}-cell ablation displayed altered lipid- and glucose-related processes. Based on the transcriptomics, we performed a genetic screen that uncovers a potential role for the molybdenum cofactor (Moco) biosynthetic pathway in {beta}-cell regeneration and glucose metabolism in zebrafish. Consistently, 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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Karampelias, C., Baloiu, B., Rathkolb, B., da Silva-Buttkus, P., Bachar-Wikstrom, E., Marschall, S., Fuchs, H., Gailus-Durner, V., Chu, L., Hrabe de Angelis, M., Andersson, O.. 2024-04-11. Characterization of liver-pancreas crosstalk following beta-cell loss reveals a role for the molybdenum cofactor in beta-cell regeneration. https://doi.org/10.1101/2024.04.09.588677

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