A Single Bout Of Exercise Decreases Fasting And Insulin-stimulated Extracellular Vesicles In Adults With Obesity

Abstract

PURPOSE: Extracellular vesicle (EV) concentrations are elevated in states of insulin resistance and may modulate type 2 diabetes and cardiovascular risk. While recent work has suggested that acute exercise reduces fasting EV concentrations, whether exercise alters EV responses to insulin is unknown. METHODS: Ten sedentary adults (5F/5M, Age: 49.5 ± 2.4 yr; VO2max: 23.9 ± 1.8 kg/mg/min) with obesity (body fat: 41.7 ± 2.3 %) completed a control and acute exercise bout condition (70% VO2max to expend 400 kcals between 4-7 pm). After an overnight fast, participants underwent a 2-hr euglycemic-hyperinsulinemic clamp (90 mg/dl; 40 mU/m2/min) to determine metabolic insulin sensitivity (M-value) and EV concentrations. Endothelial (CD105+, CD41-/CD31+), leukocyte (CD45+), platelet (CD41+, CD41+/31+), and tetraspnain-derived EVs (TX+), as well as platelet endothelial cell adhesion molecule (CD31+) were detected in platelet poor plasma samples at 0 and 2-hr of the clamp using spectral flow cytometry. Statistical significance was accepted as P ≤ 0.05. RESULTS: Exercise decreased fasting CD41-/31+ (P = 0.05), CD45+ (P = 0.04), CD41+ (P < 0.001), CD41+/31+ (P = 0.001), CD31+ (P = 0.001), and TX+ (P < 0.001) compared to rest. In addition, exercise tended to promote a greater reduction in insulin-stimulated CD31+ and TX+ (both P = 0.06) and increased the M-value compared to rest (3.68 ± 0.69 vs 2.94 ± 0.49 mg/kg/min, P = 0.03). While there were no relations among rest EVs and M-value, fasting exercise concentrations of CD105+ (r = 0.89, P = 0.001), CD41-/CD31+ (r = 0.89, P = 0.001), CD45+ (r = 0.87, P = 0.001), CD41+ (r = 0.84, P < 0.01), CD41 + 31+ (r = 0.84, P < 0.01), CD31+ (r = 0.85, P < 0.01), and TX+ (r = 0.85, P < 0.01) were associated with exercise M-value. Interestingly, the increase in the M-value following exercise (delta) was associated with overall lower concentrations of CD41+ (r = -0.68, P = 0.03), CD31 (r = -0.69, P = 0.03), and TX+ (r = -0.66, P = 0.04) with insulin infusion (delta: 2-0 hr). CONCLUSION: A single bout of exercise decreases fasting and insulin-stimulated EVs in conjunction with metabolic insulin sensitivity. More research is needed to understand the effects of exercise on EVs in the regulation of glucose homeostasis. Funding: ACSM Foundation Doctoral Student Research Grant (EMH); UVA LaunchPad (UE, SKM); NIH RO1 HL130296 (SKM)