Abstract
ObjectiveThe effect of insulin on blood flow distribution within muscle microvasculature has been suggested to be important for glucose metabolism. However, the “capillary recruitment” hypothesis is still controversial and relies on studies using indirect contrast‐enhanced ultrasound (CEU) methods.MethodsWe studied how hyperinsulinemia effects capillary blood flow in rat extensor digitorum longus (EDL) muscle during euglycemic hyperinsulinemic clamp using intravital video microscopy (IVVM). Additionally, we modeled blood flow and microbubble distribution within the vascular tree under conditions observed during euglycemic hyperinsulinemic clamp experiments.ResultsEuglycemic hyperinsulinemia caused an increase in erythrocyte (80 ± 25%, P < .01) and plasma (53 ± 12%, P < .01) flow in rat EDL microvasculature. We found no evidence of de novo capillary recruitment within, or among, capillary networks supplied by different terminal arterioles; however, erythrocyte flow became slightly more homogenous. Our computational model predicts that a decrease in asymmetry at arteriolar bifurcations causes redistribution of microbubble flow among capillaries already perfused with erythrocytes and plasma, resulting in 25% more microbubbles flowing through capillaries.ConclusionsOur model suggests increase in CEU signal during hyperinsulinemia reflects a redistribution of arteriolar flow and not de novo capillary recruitment. IVVM experiments support this prediction showing increases in erythrocyte and plasma flow and not capillary recruitment.
Highlights
The skeletal muscle vasculature delivers insulin and glucose to mus‐ cle cells, and skeletal muscle capillarization is an important contrib‐ uting factor to insulin sensitivity.[1]
Our experiments, using intravital video microscopy (IVVM) to quantify microvas‐ cular blood flow in the rat exten‐ sor digitorum longus (EDL) muscle, confirm that an increased insulin concentration while infusing glucose to maintain a fixed blood glucose level does result in increased red blood cells (RBC) velocity, RBC supply rate, and RBC flow (Figures 2A and 3F,A; but in contrast to previous reports using indirect methods,[2,3,4,5,6,7] we found no evidence of de novo capillary recruitment, either within individual capillary networks (Figure 4) or among networks supplied by different ter‐ minal arterioles (Figure 5)
Hyperinsulinemia results in more homogeneous distribution of RBC flow, but there is no evidence of a redistribution of plasma flow and no evidence that insulin regulates its own distribution and that of glucose
Summary
The skeletal muscle vasculature delivers insulin and glucose to mus‐ cle cells, and skeletal muscle capillarization is an important contrib‐ uting factor to insulin sensitivity.[1]. The primary objective of the present study was to perform euglycemic hyperinsulinemic clamp experiments on rats for the first time com‐ bined with IVVM analysis of the microcirculation in the EDL muscle to test whether hyperinsulinemia leads to capillary recruitment and redistribution of microvascular blood flow in skeletal muscle. The mean RBC velocity increased from baseline to the steady‐state portion of the hyperinsulinemic euglycemic clamp, there was no change in the total number of capillaries containing RBCs (P = .32, Figure 4A). Consistent with the 20X capillary density data, two representative functional images of over‐ lapping FOV at 10X generated from 1‐minute video sequences at baseline and 20 minutes after starting the insulin infusion show that there was no recruitment of new capillaries with RBC flow (Figure 5 and Suppinfo S1 442‐nmVideos). The modeled flow change results in a 25% increase in microbubbles in the capillary bed with a negligible change in microvascular blood volume (
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