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Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration.
- Source :
-
Life science alliance [Life Sci Alliance] 2024 Aug 19; Vol. 7 (11). Date of Electronic Publication: 2024 Aug 19 (Print Publication: 2024). - Publication Year :
- 2024
-
Abstract
- 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.<br /> (© 2024 Karampelias et al.)
- Subjects :
- Animals
Mice
Regeneration genetics
Pancreas metabolism
Pancreas cytology
Zebrafish Proteins genetics
Zebrafish Proteins metabolism
Zebrafish
Insulin-Secreting Cells metabolism
Pteridines metabolism
Coenzymes metabolism
Molybdenum Cofactors
Liver metabolism
Liver cytology
Metalloproteins metabolism
Metalloproteins genetics
Hepatocytes metabolism
Glucose metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2575-1077
- Volume :
- 7
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Life science alliance
- Publication Type :
- Academic Journal
- Accession number :
- 39159974
- Full Text :
- https://doi.org/10.26508/lsa.202402771