Lack of beta-catenin in early life induces abnormal glucose homeostasis in mice.
OBJECTIVE
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
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.
Dabernat
S
S
Department of Immunology, The Scripps Research Institute, La Jolla, CA, USA. sandrine.dabernat@u-bordeaux2.fr
Secrest
P
P
Peuchant
E
E
Moreau-Gaudry
F
F
Dubus
P
P
Sarvetnick
N
N
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism*; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017353:Gene Deletion; D006943:Hyperglycemia / Q000235:genetics; D006946:Hyperinsulinism / Q000235:genetics; D007003:Hypoglycemia / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D051176:beta Catenin / Q000172:deficiency* / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; D051176:beta Catenin; D004247:DNA