|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.
|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|
|PubMed:||22084084 Full text @ Proc. Natl. Acad. Sci. USA|
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.
ABSTRACTPancreatic 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.