Fig. 8: FXYD2^High HILOs restores euglycemia in diabetic mice in vivo.

a Secreted Gaussia luciferase and intracellular firefly luciferase activity in each HILOs is shown. Individual HILO insulin secretion was measured by the Gaussia Nano-Luc system and intracellular FXYD2 gene activity was measured by firefly luciferase. n = 48. b Correlation of secreted Gaussia Nano-Luc and intracellular FXYD2 promoter driven firefly luciferase. XY analyses is shown by simple linear regression. R² = 0.509, p < 0.0001. c INSULIN promoter driven GFP (green), FXYD2 promoter driven mCherry and optical image of isolated FXYD2 enriched (FXYD2^High) and less enriched (FXYD2^Low) HILOs (scale bars = 300 μm). d Human insulin secretion (mU/L/10,000 cells) from FXYD2^High and FXYD2^Low HILOs. n = 9. Unpaired two-tailed t-tests. e Schematic of transplantation. f Fed ad lib, blood glucose levels in 500 clusters (~1500 IEQ) of FXYD2^High (n = 6), FXYD2^Low (n = 5) or Sham (n = 2) transplanted STZ-NOD-SCID mice for ~12 weeks. Graft removal (nephrectomy, Nx) was performed on day 84 post-transplantation. Two-way ANOVA. g % of body weight change during the transplantation study is shown. FXYD2^High (n = 6), FXYD2^Low (n = 5) or sham (n = 2). Unpaired two-tailed t-tests. h Serum human c-peptide levels (pM) were measured before and 15 min after i.p. glucose injection at 8 weeks after transplantation. The right panel shows the stimulation index to GSIS (fold). FXYD2^High (n = 6), FXYD2^Low (n = 5). Unpaired two-tailed t-tests. i Representative immunofluorescence images of insulin (green) and FXYD2 (red) in transplanted kidney sections 84 days after transplantation (scale bars = 100 μm). G3 = Glucose 3 mM, G20 = Glucose 20 mM. Error bars indicate SEM.