A Clinically Applicable Positive Allosteric Modulator of GABA Receptors Promotes Human β-Cell Replication and Survival as well as GABA’s Ability to Inhibit Inflammatory T Cells
Alprazolam reduces islet cell apoptosis in human islet xenografts. Mice receiving human islet grafts were treated IP with vehicle or alprazolam (0.25 or 0.75 mg/kg/day IP) and/or GABA through their drinking water (6 mg/ml) or water alone. The frequency of apoptotic cells in the different groups of recipients was determined by TUNEL and anti-insulin staining assays. All control and experimental groups were tested side by side. Data are a representative image (magnification ×400) or expressed as the mean % of apoptotic islet of each group (-6 mice) from four islet donors in four separate experiments (with one islet donor for each experiment). (a) A representative image of apoptotic islet cells (red) and insulin+β-cells (green) in human islet grafts. Scale bar = 25 μm. (b) Frequency of apoptotic cells. (c) Frequency of insulin+β-cells. White arrows indicate apoptotic cells. ,, and vs. the control with vehicle injection and plain water. vs. GABA treated. vs. the alprazolam (0.25 mg/kg/day) and vs. the alprazolam (0.75 mg/kg/day).
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