RT Journal Article
SR Electronic
T1 Examining the liver–pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202402771
DO 10.26508/lsa.202402771
VO 7
IS 11
A1 Karampelias, Christos
A1 Băloiu, Bianca
A1 Rathkolb, Birgit
A1 da Silva-Buttkus, Patricia
A1 Bachar-Wikström, Etty
A1 Marschall, Susan
A1 Fuchs, Helmut
A1 Gailus-Durner, Valerie
A1 Chu, Lianhe
A1 Hrabě de Angelis, Martin
A1 Andersson, Olov
YR 2024
UL http://www.life-science-alliance.org/content/7/11/e202402771.abstract
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.