Insulin-mediated capillary recruitment : regulatory and anatomical aspects
Creators: name: Zhang, Lei
Publisher: name: University Of Tasmania
Year: 2023

description: Insulin-mediated increase in total blood flow has been proposed to be an important factor in determining insulin-mediated glucose uptake in skeletal muscle. However, not all researchers have seen an effect of insulin on limb blood flow in humans when the concentration of insulin and the time of exposure to hyperinsulinemia are physiologically meaningful. Recently, it has been revealed that insulin has a second hemodynamic action in skeletal muscle to recruitment rnicrovascular perfusion, an effect that is dissociable from increases in total blood flow. This micro vascular action of insulin has been demonstrated to occur at a physiological dose of insulin and precede insulin-mediated increase in bulk blood flow. In conjunction with our observations in the constant-flow pump-perfused rat hindlimb that flow redistribution between nutritive and non-nutritive routes is able to control muscle metabolism, we proposed that a capillary recruitment resulting from flow redistribution by insulin rather than increase in total flow has physiological significance in determining insulin-mediated glucose uptake in muscle. The aims of the thesis were twofold. The first was to investigate the regulatory aspects of insulin-mediated capillary recruitment in relation to insulin-mediated increase in total blood flow and glucose uptake. To this end, hyperinsulinemia euglycemic clamps were performed in anaesthetized rats. Femoral blood flow was measure by Transonic flow probe. Capillary recruitment was determined by 1-MX metabolism and contrast-enhanced ultrasound (CEU). Hindleg glucose uptake and muscle glucose uptake were also determined. In response to various doses of insulin, capillary recruitment showed a higher sensitivity to plasma insulin than total blood flow and muscle glucose uptake. In response to a termination of a physiological hyperinsulinemia, the reversal of insulin-mediated capillary recruitment had a similar time-course with that of total blood flow but slower than the reversal of insulinmediate glucose uptake. In response to TNFa, insulin-mediated capillary recruitment and glucose uptake showed a close coupling; both were opposed at low but not high insulin concentrations. The second aspect of the thesis was to seek anatomical evidence that insulin-mediated capillary recruitment may result from a redistribution of flow from non-nutritive vessels to nutritive capillaries. In the constant-flow pumpperfused rat hindlimb, flow routes were mapped using either perfusion fixation with glutaraldehyde or fluorescent dextran under basal, predominantly nutritive or nonnutritive conditions created by vasoconstrictors. The results suggest that non-nutritive vessels are on average of greater diameter than capillaries and found in connective tissue between the fibres. Overall, these findings support a physiological contribution of insulin-mediated capillary recruitment to insulin-stimulated glucose uptake and suggest that total flow and capillary recruitment are regulated by insulin via different mechanisms. Insulinmediated capillary recruitment may result from flow redistribution from non-nutritive connective vessels to nutritive capillaries.