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

Fig. 6. α-IAPP-O improves human islet graft function in diabetic mice.

Fig. 6

a Experimental design to evaluate chα-IAPP-O pharmacological efficacy in human islet-engrafted NSG (b, c) and Rag2 null mouse models (d–i). Recurrence of hyperglycemia in NSG recipient mice treated with mouse chimeric α-IAPP-O (chα-IAPP-O, 10 mg/kg) and IgG control (chIgG, 10 mg/kg) measured as blood glucose levels (b) and percentage normoglycemic animals with blood glucose values < 13 mM (c). Data in (b, c) are from three independent experiments using human islets preparations from three non-diabetic donors (Supplementary Table 2) and final group numbers were n = 13 chIgG and n = 14 chα-IAPP-O. d Blood glucose concentration during oGTT, e fasting blood glucose and, f plasma insulin levels at baseline and 14 weeks post-transplant in HFD-fed Rag2−/− recipient mice treated with chα-IAPP-O (10 mg/kg) and chIgG control (10 mg/kg) for 12 weeks (14 weeks post-transplant). Naïve Rag2−/− recipients kept on regular diet (RD) served as controls. (g) Body weight of Rag2-/- recipient mice described in (d–f) expressed as percent increase from baseline. Data in (d–g) are from two independent experiments using human islets preparations from pre-diabetic donors #5 and #6 (Supplementary Table 2) and final group numbers were n = 9 chIgG (n = 8 in f), n = 6 chα-IAPP-O and n = 2 control. h Change from baseline for glucose AUC from oGTT, (i) fasting glucose, and (j) immunofluorescence analysis of human islet grafts in HFD-induced diabetic Rag2−/− recipient mice treated with chα-IAPP-O (10 mg/kg, n = 4) and chIgG (10 mg/kg, n = 4) for 6 weeks (baseline at 8 weeks post-transplant). Human islets were isolated from a pre-diabetic donor #2 (Supplementary Table 2). (j) Representative images of human islet grafts from (d–h) and quantitative analysis stained for α-IAPP-O-positive oligomers (blue) and ThioS-positive amyloid (green). Scale bars: 100 and 20 µm. Data are expressed as means ± s.e.m. Statistical analysis was done using repeated measures ANOVA followed by Sidak’s post hoc test (b, d, h), Log-rank Mantel-Cox test (c), two tailed unpaired t test (e, f, h), or one tailed Wilcoxon Signed Rank Test (g, i). *p < 0.05 (b, c, e, h); **p < 0.01 (d, f); #p = 0.060 (i) and #p = 0.058 (j). STZ streptozotocin, HFD high fat diet.