ZFIN ID: ZDB-PUB-111122-16
Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation
Rovira, M., Huang, W., Yusuff, S., Shim, J.S., Ferrante, A.A., Liu, J.O., and Parsons, M.J.
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
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.
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