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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adipocytes / cytology
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Adipocytes / metabolism
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Animals
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Apoptosis
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Blood Glucose / metabolism
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Carrier Proteins / metabolism*
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Cell Division
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Gene Expression Regulation
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Glucose / metabolism
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Glucose Intolerance
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Homeodomain Proteins*
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Homeostasis
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Insulin / blood
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Insulin / metabolism
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Insulin Secretion
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Islets of Langerhans / cytology
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Islets of Langerhans / metabolism*
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Islets of Langerhans / physiology*
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Leptin / blood
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Male
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Mice
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Mice, Knockout
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Muscle, Smooth / cytology
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Muscle, Smooth / metabolism
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Pancreas / cytology
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Pancreas / growth & development*
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RNA-Binding Proteins
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Time Factors
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Trans-Activators / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Blood Glucose
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Carrier Proteins
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Homeodomain Proteins
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Insulin
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Leptin
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PA2G4 protein, human
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RNA-Binding Proteins
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Trans-Activators
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pancreatic and duodenal homeobox 1 protein
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Glucose