FIG. 4.

GABA_A-R and GABA_B-R activation promotes human β-cell replication in transplanted islets. Hyperglycemic NOD/scid mice were transplanted with human islets under the kidney capsule and randomly treated as described in the research design and methods. All islets recipients became normoglycemic within 2 days after transplantation and remained so during the observation period. The replication of human β-cells in the islet grafts was characterized by immunofluorescent assays using PE–anti-BrdU and fluorescein isothiocyanate–anti-insulin, followed by counterstaining with DAPI. A: The percentages of BrdU⁺insulin⁺ β-cells in the islet grafts. B: The percentages of insulin⁺ β-cells in the grafts. In another set of experiments, the kidney tissue sections (5 μm) were subjected to immunofluorescent analysis of BrdU⁺insulin⁺ and Ki67⁺insulin⁺ human β-cells using PE–anti-human Ki67. C: The percentages of Ki67⁺insulin⁺ β-cells. Data are expressed as the mean ± SEM of the percentages of BrdU⁺insulin⁺, Ki67⁺insulin⁺, or insulin⁺ islet cells in different groups of mice (N = 4–9 mice/group) from three separate experiments. Significantly higher percentages of BrdU⁺insulin⁺ or insulin⁺ islet cells were observed in the GABA-treated grafts (data not shown). *P < 0.05, **P < 0.01 vs. the water group.