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 β 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.
| Original language | English |
|---|---|
| Pages (from-to) | 1288-1295 |
| Number of pages | 8 |
| Journal | Journal of Clinical Investigation |
| Volume | 113 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2004 May |
| Externally published | Yes |
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ASJC Scopus subject areas
- Medicine(all)
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Impaired pancreatic growth, β cell mass, and β cell function in E2F1-7-/- mice. / Fajas, Lluis; Annicotte, Jean Sébastien; Miard, Stéphanie; Sarruf, David; Watanabe, Mitsuhiro; Auwerx, Johan.
In: Journal of Clinical Investigation, Vol. 113, No. 9, 05.2004, p. 1288-1295.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Impaired pancreatic growth, β cell mass, and β cell function in E2F1-7-/- mice
AU - Fajas, Lluis
AU - Annicotte, Jean Sébastien
AU - Miard, Stéphanie
AU - Sarruf, David
AU - Watanabe, Mitsuhiro
AU - Auwerx, Johan
PY - 2004/5
Y1 - 2004/5
N2 - 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 β 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.
AB - 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 β 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.
UR - http://www.scopus.com/inward/record.url?scp=2342593385&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2342593385&partnerID=8YFLogxK
U2 - 10.1172/JCI200418555
DO - 10.1172/JCI200418555
M3 - Article
C2 - 15124020
VL - 113
SP - 1288
EP - 1295
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 9
ER -