Fig 1: NogoR has marginal effects on glucose clearance and insulin sensitivity in db/db mice.a Body weights of db/db cohort pre-NogoR treatment n = 4–5. b–d Body weights, blood glucose levels and Area Under the Curve (AUC) after an oral glucose load (2 g/kg) 4 weeks after continuous NogoR treatment. n = 4–5. e, f Corresponding plasma insulin levels and AUC after oral glucose load (2 g/kg) shown in b. n = 4–5 per group. g, h Circulating glucose levels and corresponding AUC after receiving an intraperitoneal injection of 1 IU/kg of insulin. i Circulating NogoR levels 4 weeks after continuous treatment. Data are mean ± SEM. Source data are provided as a Source Data file. Data in b, e, and g were analyzed by multiple unpaired Student’s t-test, and those in a, c, d, f, h, i by Mann–Whitney test. No significant statistical differences were detected.
Fig 2: NogoR enhances glucose clearance and insulin sensitivity in HFD mice.Two separate cohorts of wild-type male C57BL/6 J mice were maintained on a high-fat diet for 6 weeks, then injected for 14 consecutive days with saline or 100 ng (2.1 pmol/animal) recombinant NogoR. a, b Body weights of cohort one and circulating glucose levels during an oral glucose tolerance test (OGTT;2 g/kg) pre-NogoR treatment n = 5. c, d Body weights and blood glucose levels after an oral glucose load (2 g/kg) of cohort one after NogoR treatment. n = 5. d **p = 0.0013; *p = 0.023 by multiple unpaired t-test. AUC **p = 0.0021 by two-tailed unpaired Student’s t-test. e Plasma insulin levels after an oral glucose load (2 g/kg) in cohort 1. n = 5 per group. f, g Post-treatment body weights of cohort 2 (n = 5 mice) and circulating glucose levels after receiving an intraperitoneal injection of 1 IU/kg of insulin. (i) *p = 0.0462 by multiple unpaired Student’s t-test. Data are mean ± SEM. Source data are provided as a Source Data file.
Fig 3: Impact of identified biomarkers on apoptosis (a–c) (n = 4 replicates from four independent mouse islet preparations; 16 mice per preparation) or proliferation (n = 4 individual donors for human islets) (d) in mouse or human islets as indicated.Test compounds were added at 100 nM unless otherwise indicated. a ***p < 2.2·10-16 for the effects of NogoR vs vehicle and ***p = 5.45·10-8 for the effects of IL18Ra vs vehicle; b *p = 0.0196, 0.0117 for the effects of 3 nM and 10 nM NogoR, respectively versus vehicle by one-way ANOVA; ***p = 1.67·10-6 and p < 2.2·10-16 for the effects of 30 and 100 nM NogoR, respectively. c ***p = 0.0009; d ***p = 0.0015. The DYRK1A/DYRK2/CLK kinase inhibitor leucettine L4186 was used as a positive control. Error bars represent means ± S.D. See Methods for other details. Source data are provided as a Source Data file.
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