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PMID: 15124020 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Impaired pancreatic growth, beta cell mass, and beta cell function in E2F1 (-/- )mice.

The Journal of clinical investigation ·Vol. 113 ·No. 9 ·2004-05-00 ·Pages 1288-95

Fajas L, Annicotte JS, Miard S, Sarruf D, Watanabe M, Auwerx J

Abstract

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Adipocytes/cytology,metabolism Animals Apoptosis Blood Glucose/metabolism Carrier Proteins/metabolism Cell Division Gene Expression Regulation Glucose/metabolism Glucose Intolerance Homeodomain Proteins Homeostasis Insulin/blood,metabolism Insulin Secretion Islets of Langerhans/cytology,metabolism,physiology Leptin/blood Male Mice Mice, Knockout Muscle, Smooth/cytology,metabolism Pancreas/cytology,growth & development RNA-Binding Proteins Time Factors Trans-Activators/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Blood Glucose Carrier Proteins Homeodomain Proteins Insulin Leptin PA2G4 protein, human RNA-Binding Proteins Trans-Activators pancreatic and duodenal homeobox 1 protein Glucose
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Fajas Lluis
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
Miard Stéphanie
Sarruf David
Watanabe Mitsuhiro
Auwerx Johan
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI18555
Published
2004-05-00
Pages
1288-95
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC398423
Subset
IM
Grants
NIDDK NIH HHS · P01 DK059820 · United States
NIDDK NIH HHS · 1P01 DK-59820-01 · United States
External Links
PubMed source DOI: 10.1172/JCI18555 PMC Full Text View journal details
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