ABMES

Background: The quantity and proliferative capacity of pancreatic β-cells have been shown to impact diabetes development, but their proliferative capacity and regulatory mechanism remain unclear. We examined the sequential changes in the proliferative ability of rat β-cells and the factors that contribute to these changes during the post-natal to young adult period.

Methods: Pancreases of Sprague Dawley rats were collected at different times (1 day-8 weeks); pancreatic β-cell proliferation was analyzed using fluorescence immunostaining. Expression of cell cycle-related genes and proteins in pancreatic β-cells was examined using quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blotting, respectively. Six-week-old rats were administered the p53 inhibitor pifithrin-α intraperitoneally for 2 weeks to clarify the relationship between the loss of β-cell proliferation and p53.

Results: The percentages of Ki67- and phosphorylated histone H3 (PhH3)-positive cells in pancreatic and duodenal homeobox factor 1 (PDX1) positive β-cells were 8.5% and 1.9%, respectively, in 1-day-old rats (2% and 0.07% of cells were Ki67- and PhH3-positive at 8 weeks). p53 mRNA and protein expression levels increased significantly in the pancreas at 8 weeks. Treatment with the p53 inhibitor for 2 weeks remarkably attenuated the decrease in the percentage of PhH3-positive β-cells at 8 weeks.

Conclusion: Rat β-cells lose their proliferative ability after birth through upregulation of p53.