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. 2023 Feb 9;14:709. doi: 10.1038/s41467-023-36148-1

Fig. 6. Glucoregulatory effects of AdEVs in mice.

Fig. 6

DIO AdEVs were isolated from male C57BL/6 J DIO mice subjected to HFD for 4–6 months a–d, g. All recipient mice a–g were male C57BL/6 J mice. a Insulin secretion in mice (12 weeks of age, n = 7 mice) at baseline and 2.5 min after glucose stimulation following a 4 hrs pretreatment with vehicle or 50 μg DIO AdEVs. b–h Glucose excursions (left panels) and corresponding area under curve (AUC, right panels) values following an b ipGTT in lean mice, 4 hrs after ip. pretreatment with vehicle vs. 10 or 50 μg of DIO AdEVs (n = 6 mice, 12 weeks of age), c, d ipGTT in lean mice, 4 hrs (c: n = 7 vehicle treated mice, n = 5 AdEV treated mice) or 36 hrs (d: n = 7 vehicle treated mice, n = 8 AdEV treated mice) after iv. pretreatment with vehicle vs. 50 μg of DIO AdEVs. e, f Glucose excursions and AUCs in lean mice 4 hrs after pre-treatment with vehicle or 50 μg of serum EVs isolated from 4-6 months old male C57BL/6 J DIO e or lean mice f (n = 8 mice in both experiments). g ipGTT in DIO recipient mice (3 months HFD, average body weight 45.5 g) and age-matched lean mice (average body weight 32.1 g), 4 hrs after ip. pretreatment with vehicle vs. 50 μg of DIO AdEVs (n = 7 mice). h ipGTT in lean 30-weeks-old male C57BL/6 J mice injected daily for 16 days with the small molecule exosome secretion inhibitor GW4869 (1 mg/kg), or vehicle (5% DMSO in 0.9% NaCl), n = 8 mice. d, e Data are presented as mean values ± SEM. Asterisks indicate *P < 0.05, **P < 0.01, ***P < 0.001. Significance was determined by two-way ANOVA and Sidak’s multiple comparisons test or unpaired two-sided t-test for AUC values. Exact P values of treatment vs. control are a adjusted P = 0.01, b P = 0.0247 (vehicle vs. 50 μg DIO AdEVs, 0 min), P = 0.002 (vehicle vs. 50 μg DIO AdEVs, 30 min), P = 0.0144 (10 μg DIO AdEVs vs. 50 μg DIO AdEVs, 30 min), P = 0.0289 (vehicle vs. 50 μg DIO AdEVs, 60 min), P = 0.0193 (10 μg DIO AdEVs vs. 50 μg DIO AdEVs, 60 min) and P = 0.0071 (for AUC Glucose), d P = 0.0275, e P = 0.0272 (15 min), P = 0.0025 (30 min) and P = 0.0127 (for AUC Glucose), g P = 0.0348 (lean + vehicle vs. DIO + vehicle, 0 min), P = 0.0143 (lean + vehicle vs. DIO + vehicle, 15 min), P = 0.0005 (lean + vehicle vs. DIO + 50 μg DIO AdEVs, 15 min), P = 0.0009 (lean + vehicle vs. DIO + vehicle, 60 min), P = 0.0043 (lean + vehicle vs. DIO + 50 μg DIO AdEVs, 60 min), P = 0.0271 (lean + vehicle vs. DIO + vehicle, 120 min), P = 0.0001 (lean + vehicle vs. DIO + 50 μg DIO AdEVs, 120 min) and P = 0.017 (for AUC Glucose), h P = 0.032 and P = 0.0238 (for AUC Glucose).