PUBLICATION
Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation
- Authors
- Rovira, M., Huang, W., Yusuff, S., Shim, J.S., Ferrante, A.A., Liu, J.O., and Parsons, M.J.
- ID
- ZDB-PUB-111122-16
- Date
- 2011
- Source
- Proceedings of the National Academy of Sciences of the United States of America 108(48): 19264-9 (Journal)
- Registered Authors
- Ferrante, Anthony A., Parsons, Michael
- Keywords
- progenitor, Notch-signaling, develolpment, embryogenesis
- MeSH Terms
-
- Acetanilides/pharmacology
- Animals
- Animals, Genetically Modified
- Caffeic Acids/pharmacology
- Cell Differentiation/drug effects*
- Cell Line, Tumor
- Cell Proliferation
- DNA Primers/genetics
- Dimethyl Sulfoxide
- Dose-Response Relationship, Drug
- Drug Discovery/methods*
- Epirizole/pharmacology
- Fluorescent Antibody Technique
- Green Fluorescent Proteins
- Guanosine Triphosphate/biosynthesis
- HMGB1 Protein/metabolism
- Insulin-Secreting Cells/cytology*
- Insulin-Secreting Cells/drug effects*
- Larva/drug effects
- Microscopy, Confocal
- Mycophenolic Acid/pharmacology
- Pharmaceutical Preparations/metabolism*
- Real-Time Polymerase Chain Reaction
- Sulfanilic Acids/pharmacology
- Tretinoin/metabolism
- Zebrafish
- p-Aminoazobenzene/analogs & derivatives
- p-Aminoazobenzene/pharmacology
- PubMed
- 22084084 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Rovira, M., Huang, W., Yusuff, S., Shim, J.S., Ferrante, A.A., Liu, J.O., and Parsons, M.J. (2011) Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation. Proceedings of the National Academy of Sciences of the United States of America. 108(48):19264-9.
Abstract
Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping