Glucose is necessary for embryonic pancreatic endocrine cell differentiation

Ghislaine Guillemain, Gaëlle Filhoulaud, Gabriela Da Silva-Xavier, Guy A Rutter, Raphaël Scharfmann

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


Mature pancreatic cells develop during embryonic life from endodermal progenitors, and this developmental process depends on activation of a hierarchy of transcription factors. While information is available on mesodermal signals controlling pancreas development, little is known about environmental factors, such as the levels of nutrients including glucose, that may control this process. Here, we studied the effects of glucose on pancreatic cells development. We used an in vitro model where both endocrine and acinar cells develop from early pancreatic and duodenal homeobox-1 (PDX1)-positive embryonic pancreatic progenitors. We first showed that glucose does not have a major effect on global pancreatic cell proliferation, survival, and acinar cell development. On the other hand, glucose controlled both alpha and beta cell development. Specifically, the surface occupied by insulin-positive cells was 20-fold higher in pancreases cultured in presence than in absence of glucose, and this effect was dose-dependent over the range 0.5-10 mm. Glucose did not appear to control beta cell development by activating the proliferation of early progenitors or beta cells themselves but instead tightly regulated cell differentiation. Thus, glucose did not modify the pattern of expression of Neurogenin3, the earliest marker of endocrine progenitor cells, but was necessary for the expression of the transcription factor NeuroD, a direct target of Neurogenin3 known to be important for proper pancreatic endocrine cell development. We conclude that glucose interferes with the pancreatic endocrine cells development by regulating the transition between Ngn3 and upstream NeuroD.

Original languageEnglish
Pages (from-to)15228-37
Number of pages10
JournalJournal of Biological Chemistry
Issue number20
Publication statusPublished - 18 May 2007


  • Animals
  • Basic Helix-Loop-Helix Transcription Factors/metabolism
  • Cell Differentiation/drug effects
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endoderm/cytology
  • Female
  • Gene Expression Regulation, Developmental/drug effects
  • Glucagon-Secreting Cells/cytology
  • Glucose/metabolism
  • Homeodomain Proteins/metabolism
  • Insulin-Secreting Cells/cytology
  • Nerve Tissue Proteins/metabolism
  • Pancreas, Exocrine/embryology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Stem Cells/cytology
  • Sweetening Agents/metabolism
  • Trans-Activators/metabolism
  • Transcription, Genetic/drug effects


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