Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation

Meritxell Rovira, Wei Huang, Shamila Yusuff, Joong Sup Shim, Anthony A. Ferrante, Jun O. Liu, Michael J. Parsons

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)19264-19269
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number48
DOIs
StatePublished - Nov 29 2011

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Keywords

  • Development
  • Embryogenesis
  • Notch-signaling
  • Progenitor

ASJC Scopus subject areas

  • General

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