PUBLICATION
Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration
- Authors
- 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.
- ID
- ZDB-PUB-240820-7
- Date
- 2024
- Source
- Life science alliance 7(11): (Journal)
- Registered Authors
- Andersson, Olov, Hrabe de Angelis, Martin, Karampelias, Christos
- Keywords
- none
- MeSH Terms
-
- Animals
- Coenzymes*/metabolism
- Glucose*/metabolism
- Hepatocytes*/metabolism
- Insulin-Secreting Cells*/metabolism
- Liver*/cytology
- Liver*/metabolism
- Metalloproteins*/genetics
- Metalloproteins*/metabolism
- Mice
- Molybdenum Cofactors*
- Pancreas/cytology
- Pancreas/metabolism
- Pteridines*/metabolism
- Regeneration/genetics
- Zebrafish*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 39159974 Full text @ Life Sci Alliance
Citation
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. (2024) Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in β-cell regeneration. Life science alliance. 7(11):.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping