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. 2023 Oct 9;14:6294. doi: 10.1038/s41467-023-41986-0

Fig. 4. α-IAPP-O delays diabetes progression and improves beta-cell function in hIAPP transgenic rats.

Fig. 4

a Representative images of individual pancreatic islets from 57-week-old transgenic and wild-type rats stained for α-IAPP-O target engagement (blue), ThioS-positive islet amyloid (green) and insulin-positive beta cells (red). Scale bars: 100 and 25 µm. Similar results have been obtained in independent experiments using three different animals per genotype. b Blood glucose concentration and c plasma insulin response during oGTT in 36-week-old hIAPP transgenic rats injected with vehicle or rat chimeric α-IAPP-O (chα-IAPP-O, 3 mg/kg), metformin alone (met; 200 mg/kg/day) or in combination with 3 mg/kg chα-IAPP-O (chα-IAPP-O+met) for 24 weeks. Group size for 4b-c were n = 14 vehicle, n = 14 met, n = 16 chα-IAPP-O, n = 13 chα-IAPP-O+met. d Blood glucose and e plasma insulin levels during oGTT in 50-week-old transgenic rats administered with chα-IAPP-O at 1, 3, and 10 mg/kg for 38 weeks compared to vehicle. f Beta cell function in rats after 38 weeks of treatment. g Longitudinal blood glucose levels, (h) HbA1c and (I) non-fasting plasma insulin in transgenic rats after 41 weeks of treatment. Group size for (d–i), and (l) were n = 18 vehicle, n = 19 chα-IAPP-O 1 mg/kg, n = 16 chα-IAPP-O 3 mg/kg, n = 18 chα-IAPP-O 10 mg/kg. For (f, g) group averages from individual animals are shown. Representative images (j) and quantitative analysis (k) of pancreatic islets stained for insulin (red) and hIAPP (green; E-5 antibody) (scale bar: 100 µm), and (l) soluble IAPP and insoluble IAPP levels in pancreas homogenates after 41 weeks of treatment. Group sizes in (k) for vehicle and chα-IAPP-O 10 mg/kg are: 18/18 (mean islet area, insulin+ β-cells, β-cell mass) and 9/11 (hIAPP+ β-cells). For group sizes in (l) see above. All data are expressed as means ± s.e.m. * or σp < 0.05; ## or σσp < 0.001; ###p < 0.0001 (b, c) and * or #p < 0.05; **p < 0.01; ###p < 0.001; **** or ####p < 0.0001 by repeated measures ANOVA with Dunnett’s test post-hoc (b, c, d, e, g), one-way ANOVA with Dunnett’s post-hoc test (f, h, i, l), or two-tailed unpaired t test (k) comparing antibody/metformin-treated animals vs vehicle. ns not significant.