199-OR: Insulin Infusion Decreases Extracellular Vesicles in Adults with Metabolic Syndrome

Abstract

Elevated extracellular vesicles (EVs) are associated with glucose dysmetabolism. However, the direct effects of insulin on EVs and subsequent relationship with insulin sensitivity and substrate oxidation is unknown in adults with metabolic syndrome (MetS). Fifty sedentary adults (54.5 ± 1.0 yr; VO2peak: 22.3 ± 0.6 ml/kg/min) with MetS (36.3 ± 0.7 kg/m2; ATP III Criteria: 3.46 ± 1.0) underwent a 2-hr euglycemic-hyperinsulinemic clamp (90 mg/dl; 40 mU/m2/min) to determine EV responses to insulin and metabolic insulin sensitivity (M-Value). Endothelial (CD105+, CD41-/CD31+), leukocyte (CD45+), platelet (CD41+, CD41+/CD31+), and tetraspanin-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. Fat (Fox) and carbohydrate oxidation (CHOox) were also measured (indirect calorimetry) to determine metabolic flexibility. Despite low metabolic insulin sensitivity (2.55 ± 0.2 mg/kg/min), insulin (82.9 ± 3.7 uU/ml) reduced Fox (delta, P=0.001) compared to fasting. Insulin also decreased CD105+ (P<0.01), CD41-/CD31+ (P=0.03), CD41+ (trend: P=0.06), TX+ (P<0.01), and CD31+ (P=0.03). Surprisingly, there were no correlations between EVs and metabolic insulin sensitivity. However, higher fasting insulin levels were related to lower insulin-stimulated changes in CD105+ (r=0.32, P=0.03), CD41-/CD31+ (r=0.33, P=0.05), and CD45+ (r=0.33, P=0.04). Further, fasting TX+ and CD41+ (r=0.33, P=0.05 and r=0.42, P<0.01) were related to fasting CHOox while CD105+ was inversely associated with fasting Fox (r=-0.33, P=0.03). Fasting TX+ (r=-0.42, P=0.01), CD31+ (r=-0.33, P=0.04), and CD41+ (r=-0.32, P=0.04) also correlated with CHOox metabolic flexibility. Insulin infusion decreases EVs in adults with MetS. Additional work investigating the role of EVs on substrate metabolism is warranted to elucidate mechanisms for type 2 diabetes risk. Disclosure E. Heiston: None. A. Ballantyne: None. N. Stewart: None. L. Musante: None. U. Erdbruegger: None. S. K. Malin: None. Funding National Institutes of Health (R01HL130296)