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Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in Mice

Figure 3

Single-pulse BrdU-labeled β-cells are more frequent in diabetic mice, and correlate with ß-cell DNA-content measurements.

Naïve and diabetic mice around 20 weeks of age received a BrdU injection (10 mg/ml at 2.5 mg/mouse, i.p.). Islets were isolated the following day and 5-color stained (3-hormones, CD45+ leucocytes, and incorporated BrdU). A: Representative example of a naïve (top panel), and a newly diabetic CTL-induced EAD mouse (bottom panel). BrdU-staining is shown on the right panel, while isotype/fluorochrome controls are shown on the left. Note that BrdU incorporation (right panels) upon short-term exposure in naïve islets β-cells is very low, but increases in diabetic mice. B: Correlation plot between BrdU pulse-labeling and the frequency of increased DNA content among islet β-cells. Each symbol represents islets of a single mouse, aliquoted for independent staining of BrdU and DNA content. Three different groups of mice were tested: Rip-CD80+GP+ (naïve, open square; and diabetic, closed circles), and insulinoma-developing Rip-Tag2 mice (open triangles). Correlation coefficient r = 0.88; 95% confidence interval (dashed lines).

Figure 3

doi: https://doi.org/10.1371/journal.pone.0004827.g003