Effect of N^G‐monomethyl l‐arginine on microvascular blood flow and glucose metabolism after an oral glucose load

Abstract

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 N G -monomethyl L-arginine (L-NMMA) using microdialysis. MethodsMicrodialysis catheters, perfused with L-NMMA 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 (LSCI), and glucose metabolites were measured. ResultsAfter oral glucose intake,microvascular blood flow and glucose metabolism were both significantly suppressed in the L-NMMA catheter compared to the control catheter (urea clearance: p<0.006, glucose dialysate concentration: p<0.035). No significant effect of L-NMMA on microvascular blood flow was observed with LSCI (p=0.81). ConclusionLocal delivery of L-NMMA to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulinmediated vasodilation.

Investigation of proteins important for microcirculation using in vivo microdialysis after glucose provocation: a proteomic study

“…Microdialysis catheters (100 kDa CMA 71 and 20 kDa CMA 67, 10 mm membrane, M dialysis AB, Stockholm, Sweden) were inserted intracutaneous in the volar skin of the non-dominant forearm, subcutaneous in the periumbilical adipose tissue and intravenous in a peripheral vein in each of the eight subjects. The procedure for insertion of microdialysis catheters has previously been described in detail 8 , 9 , 14 . Before insertion, all catheters were connected to microinjection pumps (CMA 107, CMA AB, Uppsala, Sweden) and perfused for 90 min to ensure adequate function and reduce the risk of obstructing bubbles in the microdialysis tubing.…”

“…The skin has become a popular model for studying the microvascular function, because it is easily accessible and considered to be a representative vascular bed for the microcirculation 7 . Assessment of the skin microvascular function can be performed by both invasive, for instance microdialysis technique 8 , 9 , and noninvasive techniques, such as laser speckle contrast imaging (LSCI) or laser Doppler flowmetry 10 – 12 .…”

“…Substances can pass, by simple diffusion, across the dialysis membrane along a concentration gradient 13 . The metabolic and vascular effects of insulin in the human skin have previously been investigated using microdialysis technique 8 , 9 . It is known that oral glucose provocation, and thereby endogenously increased insulin, increases local tissue blood flow in the human skin.…”

Sampling insulin in different tissue compartments using microdialysis: methodological aspects

“…In eleven subjects, microdialysis catheters (CMA 71, 10 mm membrane, 100 kDa cut off, M dialysis AB, Stockholm, Sweden) were inserted intracutaneously in the volar skin of the non-dominant forearm and subcutaneously in the periumbilical adipose tissue. The procedure for catheter insertion has previously been described in detail 2,3 , and the intracutaenous catheter placement have been shown with ultrasound to be at a depth of approximately 0.8 mm depth, on the boundary of dermis and hypodermis 2,3,17 . An additional microdialysis catheter for intravenous use (CMA 67, 10 mm membrane, 20 kDa cut off, M dialysis AB, Stockholm, Sweden) was inserted in a peripheral vein in the cubital fossa.…”