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Effect of N OBJECTIVE: The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor NG -monomethyl l-arginine using microdialysis. METHODS: Microdialysis catheters, perfused with NG -monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. RESULTS: After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the NG -monomethyl l-arginine catheter compared to the control catheter (urea clearance: P < .006, glucose dialysate concentration: P < .035). No significant effect of NG -monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). CONCLUSION: Local delivery of NG -monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.