Impaired pancreatic growth, beta cell mass, and beta cell function in E2F1 (-/- )mice.
We evaluated the effects of E2F1 on glucose homeostasis using E2F1(-/-) mice. E2F1(-/-) mice show an overall reduction in pancreatic size as the result of impaired postnatal pancreatic growth. Furthermore, these animals have dysfunctional beta cells, linked to impaired PDX-1 activity. Because of the disproportionate small pancreas and dysfunctional islets, E2F1(-/-) mice secrete insufficient amounts of insulin in response to a glucose load, resulting in glucose intolerance. Despite this glucose intolerance, E2F1(-/-) mice do not develop overt diabetes mellitus because they have insulin hypersensitivity, which is secondary to a diminished adipose tissue mass and altered adipocytokine levels, which compensates for the defect in insulin secretion. These data demonstrate that factors controlling cell proliferation, such as E2F1, determine pancreatic growth and function, subsequently affecting metabolic homeostasis.
Fajas
Lluis
L
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université Louis Pasteur, Illkirch, France.
Annicotte
Jean-Sébastien
JS
Miard
Stéphanie
S
Sarruf
David
D
Watanabe
Mitsuhiro
M
Auwerx
Johan
J
D048868:Adaptor Proteins, Signal Transducing; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance; D018398:Homeodomain Proteins; D006706:Homeostasis; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000254:growth & development*; D016601:RNA-Binding Proteins; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; D002352:Carrier Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D020738:Leptin; C101633:PA2G4 protein, human; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose