PT  - JOURNAL ARTICLE
AU  - Karampelias, Christos
AU  - Băloiu, Bianca
AU  - Rathkolb, Birgit
AU  - da Silva-Buttkus, Patricia
AU  - Bachar-Wikström, Etty
AU  - Marschall, Susan
AU  - Fuchs, Helmut
AU  - Gailus-Durner, Valerie
AU  - Chu, Lianhe
AU  - Hrabě de Angelis, Martin
AU  - Andersson, Olov
TI  - Examining the liver–pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration
AID  - 10.26508/lsa.202402771
DP  - 2024 Nov 01
TA  - Life Science Alliance
PG  - e202402771
VI  - 7
IP  - 11
4099  - http://www.life-science-alliance.org/content/7/11/e202402771.short
4100  - http://www.life-science-alliance.org/content/7/11/e202402771.full
SO  - Life Sci. Alliance2024 Nov 01; 7
AB  - 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.The data that support the findings of this study are available from the corresponding authors upon reasonable request. The raw reads of the RNA-Seq data are available in the Sequence Read Archive under the accession number PRJNA1103351.