A Single Bout of Aerobic Exercise Increases Neuronal Extracellular Vesicle-Derived Insulin Signaling Biomarkers in Adults With Cardiometabolic Risk.

A single bout of aerobic exercise increased neuronal extracellular vesicle-derived insulin receptor phosphorylation (pIR-Tyr1162/Tyr1163) compared with the resting condition.

• p = 0.05, η² = 0.05 (medium effect size)
• Effect was observed across blood draws compared with the resting condition
• Study population: 15 sedentary adults with obesity (12 female, ~56 years, ~31 kg/m²)
• Exercise was performed at 70% maximal oxygen consumption (VO2max)

Acute aerobic exercise increased neuronal extracellular vesicle-derived pIRS-1-Ser636 compared with rest.

• p = 0.02, η² = 0.07 (medium effect size)
• Effect observed across blood draws in the exercise versus resting condition
• IRS-1 Ser636 phosphorylation is a component of the insulin signaling cascade
• Participants completed an evening exercise or rest condition in randomized, counterbalanced order

A single bout of aerobic exercise increased neuronal extracellular vesicle-derived pAkt-Ser473 compared with the resting condition.

• p = 0.03, η² = 0.06 (medium effect size)
• Effect was observed across multiple blood draw time points
• Blood draws were taken following an overnight fast, after intranasal insulin (40 IU), and 60 min after a 75 g oral glucose tolerance test (OGTT)

Acute aerobic exercise increased neuronal extracellular vesicle-derived pTSC2-Ser939 compared with rest.

• p = 0.01, η² = 0.08 (medium effect size)
• pTSC2-Ser939 was the strongest effect size among the upregulated insulin signaling phosphoproteins
• Effect was observed across blood draws in the exercise condition

Exercise altered the pattern of neuronal extracellular vesicle-derived pp70S6K-Thr412, raising fasting levels and decreasing post-OGTT levels, compared with increased levels after the OGTT following rest.

• p = 0.02, η² = 0.10
• η² = 0.10 was the largest effect size among all significant insulin signaling findings
• Exercise raised fasting pp70S6K-Thr412 but decreased it before and after the OGTT, contrasting with the rest condition where OGTT increased pp70S6K-Thr412

Exercise tended to lower glucose total area under the curve (tAUC0-150min) during the OGTT without affecting insulin tAUC.

• Glucose tAUC0-150min trend: p = 0.08, d = 0.50 (medium effect size)
• Insulin tAUC0-150min: p = 0.99, d = 0.00 (no effect)
• OGTT used a 75 g glucose load with plasma glucose and insulin measured at 30 and 60 min

Exercise had no significant effect on several other neuronal extracellular vesicle-derived insulin signaling proteins.

• No significant effect was found for pmTOR-Ser2448 or pGSK3β-Ser9, among others
• These null findings were noted as part of the overall pattern of selective insulin signaling pathway activation

The study design involved sedentary adults with obesity completing both an evening rest and an acute aerobic exercise condition in a randomized, counterbalanced crossover design.

• N = 15 participants (12 female, ~56 years, ~31 kg/m²)
• Exercise intensity was 70% VO2max
• Following an overnight fast, plasma was collected for nEV analysis before and after intranasal insulin spray (40 IU) and 60 min after a 75 g OGTT
• Registered under NCT05853913