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Insulin-mediated capillary recruitment : regulatory and anatomical aspects

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Zhang, Lei (2005) Insulin-mediated capillary recruitment : regulatory and anatomical aspects. PhD thesis, University of Tasmania.

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Abstract

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.

Item Type: Thesis (PhD)
Keywords: Hemodynamics, Insulin resistance, Muscles, Insulin
Copyright Holders: The Author
Copyright Information:

Copyright 2005 the Author - The University is continuing to endeavour to trace the copyright owner(s) and in the meantime this item has been reproduced here in good faith. We would be pleased to hear from the copyright owner(s).

Additional Information:

Thesis (Ph.D.)--University of Tasmania, 2005. Includes bibliographical references

Date Deposited: 04 Feb 2015 23:31
Last Modified: 24 Aug 2016 04:28
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