Repurposing Lesogaberan to Promote Human Islet Cell Survival and β-Cell Replication

Figure 2

Oral lesogaberan promotes human islet β-cell replication in mice. Mildly hyperglycemic NOD/scid mice were transplanted with human islets under their kidney capsule. The mice were randomized and provided with water containing with BrdU, with or without GABA (6 mg/ml) or lesogaberan (0.08 mg/ml) for 12 days. The percentages of replicated β-cells were determined by immunofluorescent assays using anti-insulin and anti-BrdU or anti-Ki67, followed by counterstaining with DAPI. (a) Representative image of islet cells (magnification ×400) costained with anti-insulin (green) and anti-BrdU (red) (arrows). (b) Representative image of islet cells costained with anti-insulin (green) and anti-Ki67 (red) (arrows). (c) Graphical representation of the percentages of BrdU⁺insulin⁺ β-cells and (d) Ki67⁺insulin⁺ islet cells in total insulin⁺ β-cells. Data are mean ± SEM from two independent experiments, each using islets from a human donor that were implanted into 4–9 NOD/scid mice. The percentages of BrdU⁺insulin⁺ and Ki67⁺insulin⁺ β-cells in at least 2000 islet cells of 10 fields of each islet graft were determined as described in Materials and Methods. , versus the control.

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