PUBLICATION
Artemether and aspterric acid induce pancreatic α cells to transdifferentiate into β cells in zebrafish
- Authors
- Jia, J., Kang, Q., Liu, S., Song, Y., Wong, F.S., Qiu, Y., Li, M.
- ID
- ZDB-PUB-211207-23
- Date
- 2021
- Source
- British journal of pharmacology 179(9): 1962-1977 (Journal)
- Registered Authors
- Li, Mingyu
- Keywords
- Artemether, Aspterric acid, Transdifferentiation, Zebrafish, α cells, β cells
- MeSH Terms
-
- Animals
- Artemether/metabolism
- Glucagon-Secreting Cells*/metabolism
- Heterocyclic Compounds, 3-Ring
- Insulin-Secreting Cells*/metabolism
- Zebrafish
- PubMed
- 34871457 Full text @ Br. J. Pharmacol.
Citation
Jia, J., Kang, Q., Liu, S., Song, Y., Wong, F.S., Qiu, Y., Li, M. (2021) Artemether and aspterric acid induce pancreatic α cells to transdifferentiate into β cells in zebrafish. British journal of pharmacology. 179(9):1962-1977.
Abstract
Background and purpose Recently, the anti-malarial drug, artemether, and the neurotransmitter γ-aminobutyric acid (GABA) were identified to convert α cells into β-like cells in vivo. However, some of these observations were challenged by other studies. To help address the controversy, we took advantage of zebrafish as a model to perform this study.
Experimental approach Firstly, we performed a small molecule screening for artemether and its skeleton analogs. Secondly, we used the Cre-LoxP system for lineage tracing to indicate the conversion of α cells into β cells in vivo. The stable transgenic ins2:eGFP αTC1-6 cell line were used for evaluation of α cell transdifferentiation in vitro. We further used multiple zebrafish transgenic and mutation lines to demonstrate β-cell differentiation, β-cell ablation and α-cell hyperplasia in this study.
Key results We showed that artemether and another sesquiterpene, aspterric acid, induced α cell transdifferentiation into β cells, both in zebrafish as well as using αTC1-6 cells. Furthermore, these two compounds also converted α cells into β cells when β cells were lost or α cells were hyperplastic in zebrafish. Unlike the previous report, the conversion of α cells to β cells was mediated by increasing Pax4 expression, but not suppression of Arx expression.
Conclusions and implications Our data suggest that in zebrafish and αTC1-6 cells, both artemether and aspterric acid induce α cell transdifferentiation. Our data, along with those of Li et al. (2017), suggested that artemether and aspterric acid were able to induce α cell transdifferentiation, at least in zebrafish and αTC1-6 cells.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping