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

Diabetologia. 2009 Aug;52(8):1608-17. doi: 10.1007/s00125-009-1411-y. Epub 2009 Jun 10.


Aims/hypothesis: 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 beta-catenin in pancreatic organogenesis. However, little is known about the involvement of beta-catenin in the endocrine or exocrine function of the mature pancreas. We report for the first time the impact of beta-catenin deletion in the pancreatic beta cells.

Methods: We targeted the deletion of the beta-catenin gene in pancreatic beta cells by crossing a floxed beta-catenin mouse strain with a RIP-Cre mouse strain.

Results: 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 beta-catenin affects beta cell size. Some newborns survived beta-catenin deletion and showed a milder phenotype during adulthood.

Conclusions/interpretation: The deletion of beta-catenin in the maturing beta cells negatively impacts on islet morphology and function. This work reveals that lack of beta-catenin in early life is related to severe deregulation of glucose homeostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism*
  • Crosses, Genetic
  • DNA / genetics
  • DNA / isolation & purification
  • Gene Deletion
  • Hyperglycemia / genetics
  • Hyperinsulinism / genetics
  • Hypoglycemia / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / pathology*
  • Mice
  • Mice, Inbred Strains
  • Polymerase Chain Reaction
  • beta Catenin / deficiency*
  • beta Catenin / genetics


  • Blood Glucose
  • Insulin
  • beta Catenin
  • DNA