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

First Author  Fajas L Year  2004
Journal  J Clin Invest Volume  113
Issue  9 Pages  1288-95
PubMed ID  15124020 Mgi Jnum  J:89720
Mgi Id  MGI:3041322 Doi  10.1172/JCI18555
Citation  Fajas L, et al. (2004) Impaired pancreatic growth, beta cell mass, and beta cell function in E2F1 (-/- )mice. J Clin Invest 113(9):1288-95
abstractText  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.
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