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


ABSTRACT:

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.

SUBMITTER: Dabernat S 

PROVIDER: S-EPMC4288852 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Publications

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

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

Diabetologia 20090610 8


<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>We targeted the deleti  ...[more]

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