title: Importance of β-Catenin in glucose and energy homeostasis.
abstract: In settings of increased insulin demand, failure to expand pancreatic β-cells mass leads to diabetes. Genome-wide scans of diabetic populations have uncovered several genes associated with susceptibility to type 2 diabetes and a number of them are part of the Wnt signaling. β-Catenin, a Wnt downstream effector participates in pancreatic development, however, little is known about its action in mature β-cells. Deletion of β-Catenin in Pdx1 pancreatic progenitors leads to a decreased β-cell mass and impaired glucose tolerance. Surprisingly, loss of β-catenin made these mice resistant to high fat diet because of their increased energy expenditure and insulin sensitivity due to hyperactivity. The complexity of this phenotype was also explained in part by ectopic expression of Cre recombinase in the hypothalamus. Our data implicates β-Catenin in the regulation of metabolism and energy homeostasis and suggest that Wnt signaling modulates the susceptibility to diabetes by acting on different tissues.
authors.affiliation: Department of Metabolism, Endocrine & Diabetes, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Elghazi
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Gould
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Weiss
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Barker
authors.forename: John
authors.initials: J
authors.lastname: Callaghan
authors.forename: Darren
authors.initials: D
authors.lastname: Opland
authors.forename: Martin
authors.initials: M
authors.lastname: Myers
authors.forename: Corentin
authors.initials: C
authors.lastname: Cras-Méneur
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bernal-Mizrachi
mesh_terms: D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D017353:Gene Deletion; D005947:Glucose / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose