| First Author | Karampelias C | Year | 2024 |
| Journal | Life Sci Alliance | Volume | 7 |
| Issue | 11 | PubMed ID | 39159974 |
| Mgi Jnum | J:357548 | Mgi Id | MGI:7712588 |
| Doi | 10.26508/lsa.202402771 | Citation | Karampelias C, et al. (2024) Examining the liver-pancreas crosstalk reveals a role for the molybdenum cofactor in beta-cell regeneration. Life Sci Alliance 7(11) |
| abstractText | 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, either directly or indirectly via secreted proteins or metabolites, in a zebrafish model of beta-cell loss. Using lineage tracing, we show that hepatocytes do not directly convert into beta-cells even under extreme beta-cell ablation conditions. A transcriptomic analysis of isolated hepatocytes after beta-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 beta-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. |
