Impaired pancreatic growth, β cell mass, and β cell function in E2F1 –/– mice
Lluis Fajas, … , Mitsuhiro Watanabe, Johan Auwerx
Lluis Fajas, … , Mitsuhiro Watanabe, Johan Auwerx
Published May 1, 2004
Citation Information: J Clin Invest. 2004;113(9):1288-1295. https://doi.org/10.1172/JCI18555.
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Article Metabolism

Impaired pancreatic growth, β cell mass, and β cell function in E2F1 –/– mice

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.

Authors

Lluis Fajas, Jean-Sébastien Annicotte, Stéphanie Miard, David Sarruf, Mitsuhiro Watanabe, Johan Auwerx

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Figure 4

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Pancreatic size and β cell area. (A) H&E staining of pancreatic sect...
Pancreatic size and β cell area. (A) H&E staining of pancreatic sections of E2F1_/_ or E2F1+/+ 4-week-old mice. Pancreatic islets are indicated by arrowheads. (B) Pancreatic islet number in E2F1_/_ and E2F1+/+ 4-week-old mice. Summed islet numbers obtained from examining every fifth section of 20-∝m thickness from a whole pancreas (left scale). The numbers were relative to pancreas weight to determine the islet/pancreas ratio (right scale). (C) Endocrine islet area calculated as arbitrary units (arb. units) from micrographs of pancreatic sections of E2F1+/+ or E2F1_/_ 4-week-old mice using the Canvas 7 software. The right scale represents the islet area relative to pancreas weight. (D) H&E staining of pancreatic sections of E2F1_/_ and E2F1+/+ mice. Quantification of the relative (rel.) cell size of exocrine pancreatic cells of 2-week-old E2F1_/_ and E2F1+/+ mice. (E) Immunofluorescence analysis of pancreatic sections showing expression of E2F1 in ducts and β cells (green), which are also positive for insulin (red). Nuclei are stained with the Hoechst reagent. *Statistically significant differences (ANOVA, P < 0.005).