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. 2020 Aug 20;5(16):e138034. doi: 10.1172/jci.insight.138034

Figure 1. Effects of temporal FKGK18 regimen on T1D incidence and islet phenotype.

Figure 1

Female NOD mice were administered FKGK18 (20 mg/kg, 3 × weekly) or vehicle (PBS-T) starting at 4 or 8 weeks of age. (A and B) Diabetes incidence. Blood glucose was monitored weekly in the 4-week (A; n = 17 and 15 for PBS-T and FKGK18 groups, respectively) and 8-week (B; n = 15 each in the PBS-T and FKGK18 groups) regimen groups for up to 30 weeks. Two consecutive readings of ≥ 275 mg/dL were recorded as onset of T1D (†P < 0.05). (C–F) Glucose tolerance test (GTT). Overnight fasted mice were administered glucose (2 g/kg, i.p.), glucose levels in blood from tail vein were monitored over a 2-hour period, and AUC were generated. (C and D) Four-week group at 14 weeks of age; n = 5 each in the PBS-T and FKGK18 groups. (E and F) Eight-week group at 25 weeks of age; n = 7 and 5 for PBS-T and FKGK18 groups, respectively. (G–I) Phenotype parameters in the 8-week regimen group. (G) Urinary PGE2 metabolites (PGEMs, n = 6 in each group, 18 weeks of age). (H and I) β Cell mass (PBS-T, n = 15; FKGK18, n = 14) (H) and circulating insulin (n = 15 in each group) (I) were determined at sacrifice (PBS-T, 14–30 weeks of age; FKGK18, 16–36 weeks of age). (J and K) Islet infiltration. Paraffin sections (10 μm) of pancreas were prepared and stained with H&E. Percent infiltration for each islet was calculated as the value of noninfiltrated area subtracted from total islet area (% infiltrate = 100 × [(total area – noninfiltrated area)/(total area)]) using ImageJ software. (PBS-T, n = 14 and 166 islets; FKGK18, n = 15 and 260 islets). (J) Islet Infiltration Range. (K) Average islet infiltration. (L and M) Islet immune cell phenotype. Paraffin sections (10 μm) of pancreas were prepared and stained for CD4+-T cells or B (B220) cells. Data presented are mean ± SEM of CD4+ T cells or B cells per islet. (L) Quantitation of CD4± T cells per islet (PBS-T, n = 14 and 223 islets; FKGK18, n = 15 and 290 islets). (M) Quantitation of B cells per islet (PBS-T, n = 14 and 213 islets; FKGK18, n = 15 and 328 islets). Statistical analyses: (A and B) Mantel-Cox test; (D–M) Student’s t test.