Extended Data Fig. 5: Effect of liver extracellular vesicles in regulating glucose effectiveness.
(A) Glucose area under the curve (AUC) during an oral glucose tolerance test in streptozotocin (STZ) treated mice that received an intraperitoneal injection of saline or Control liver EVs (n = 4 control saline, n = 6/group STZ) across 1 cohort. *, significant from Control + saline; #, significant from STZ + saline. P = 0.001. (B-D) Whole body calorimetry and activity in Control mice over 2 hours in response to saline or liver EVs. Fat oxidation (B, P = 0.58), energy expenditure (C, P = 0.04), and physical activity (D, P = 0.54). n = 4/group. 1 experiment. *, significant from Saline. (E) Serum insulin in STZ mice in response to saline or liver EVs, followed by gavage with vehicle (n = 8 saline/H2O) or glucose (n = 8 saline/high glucose (HG), n = 7 liver control EV/HG) 1 hr later across 2 cohorts. P = 0.245. (F) Plasma membrane CAV3 content in STZ mice in response to saline or liver EVs followed by oral gavage with vehicle (n = 8 saline/H2O) or glucose (n = 8 saline/HG, n = 9 control EV + HG) 1 hr later across 2 cohorts. P = 0.918. (G) Pathways enrichment analysis for phosphosites regulated in soleus muscle from Control mice following high glucose (HG + saline, n = 5) treatment relative to low glucose (LG + saline, n = 4) in the presence of saline. q < 0.05. (H) Pathways enrichment analysis for phosphosites regulated in soleus muscle from Control mice following high glucose treatment and liver EVs (HG + EV, n = 5) relative to HG and saline (HG + saline, n = 5). q < 0.05. (I) Glucose uptake between no drug, dantrolene (5 μM), and KN-62 (10 μM) under LG (2 μM, n = 5 no drug, n = 3 dantrolene, n = 3 KN-62) and HG (20 μM, n = 7 no drug, n = 5 dantrolene, n = 8 KN-62) conditions in soleus muscle. P < 0.001 main effect: condition. Same values reassessed from Figs. 6E and F. Data are expressed as mean ± SEM. Each data point represents an independent biological sample. Data was analysed using one-way ANOVA (A, F) and two- way repeated measures ANOVA (E) with Student Newman Keuls post-hoc, or unpaired two-tailed t-test (B, C, D, G, H).
