Lack of β-catenin in early life induces abnormal glucose homeostasis in mice

S. Dabernat, P. Secrest, E. Peuchant, F. Moreau-Gaudry, P. Dubus, N. Sarvetnick

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Wingless and iNT-1 (WNT) pathway members are critical for pancreatic development and exocrine tissue formation. Recently, much attention has focused on delineating the roles of β-catenin in pancreatic organogenesis. However, little is known about the involvement of β-catenin in the endocrine or exocrine function of the mature pancreas. We report for the first time the impact of β-catenin deletion in the pancreatic beta cells. We targeted the deletion of the β-catenin gene in pancreatic beta cells by crossing a floxed β-catenin mouse strain with a RIP-Cre mouse strain. Surprisingly, the majority of the mutant mice died shortly after birth and had deregulated glucose and insulin levels. The newborn mutant pancreases demonstrated increased insulin content, reflecting a defect in insulin release confirmed in vitro. Moreover, there was a reduction in total endocrine tissue at birth, while cellularity in islets was greater, suggesting that lack of β-catenin affects beta cell size. Some newborns survived β-catenin deletion and showed a milder phenotype during adulthood. The deletion of β-catenin in the maturing beta cells negatively impacts on islet morphology and function. This work reveals that lack of β-catenin in early life is related to severe deregulation of glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)1608-1617
Number of pages10
JournalDiabetologia
Volume52
Issue number8
DOIs
StatePublished - Aug 2009

Keywords

  • Beta cell
  • Beta-catenin
  • Insulin secretion
  • Pancreas
  • WNT

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Dabernat, S., Secrest, P., Peuchant, E., Moreau-Gaudry, F., Dubus, P., & Sarvetnick, N. (2009). Lack of β-catenin in early life induces abnormal glucose homeostasis in mice. Diabetologia, 52(8), 1608-1617. https://doi.org/10.1007/s00125-009-1411-y