Hyperinsulinemic-euglycemic clamp increases glycocalyx thickness in young, healthy participants

The endothelial glycocalyx is hypothesized to regulate insulin-mediated microvascular recruitment, facilitating glucose uptake, although it is unknown if this acutely promotes glycocalyx synthesis. Here, we sought to determine whether hyperinsulinemic-euglycemic clamp alters glycocalyx properties in young, healthy adults. Nine young, healthy adults (20±3 yr) underwent assessment of glycocalyx and microcirculatory properties using intravital microscopy before and during hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp increased glycocalyx thickness (P<0.05), whereas glycocalyx integrity was unchanged (P>0.05). Additionally, microvascular recruitment capacity, capillary blood volume dynamic, and red blood cell velocity were reduced during hyperinsulinemic-euglycemic clamp (P<0.05), whereas perfused microvascular density and microvascular flow were unchanged (P>0.05). Exploratory analyses were performed after grouping participants according to insulin sensitivity, determined by glucose infusion rate (GIR) normalized to fat-free mass (FFM). Participants with higher insulin sensitivity (GIR ≥5.0 mg/kg FFM/min) demonstrated an increase in glycocalyx thickness (P<0.05) with no change in glycocalyx integrity (P>0.05) following hyperinsulinemic-euglycemic clamp. In contrast, participants with lower insulin sensitivity (GIR <5.0 mg/kg FFM/min) demonstrated no change in glycocalyx thickness or glycocalyx integrity (P>0.05) following hyperinsulinemic-euglycemic clamp. These findings demonstrate that the endothelial glycocalyx undergoes rapid structural remodeling during hyperinsulinemic-euglycemic clamp in healthy humans. Acute hyperinsulinemia was also associated with alterations in microvascular hemodynamics despite preserved microvascular flow, suggesting that glycocalyx remodeling may occur in parallel with changes in microcirculatory function. Moreover, exploratory subgroup analyses suggested that glycocalyx responsiveness to hyperinsulinemia may differ according to insulin sensitivity, suggesting that glycocalyx responsiveness may represent a previously unrecognized component of metabolic health.