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Muscle fuel uptake : a result of hormone and substrate interaction affecting regional blood flow


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Clerk, Lucy Henrietta 2001 , 'Muscle fuel uptake : a result of hormone and substrate interaction affecting regional blood flow', PhD thesis, University of Tasmania.

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Substantial evidence now exists for two distinct vascular circuits within skeletal muscle.
The nutritive capillary circuit directly nourishes skeletal myocytes, whereas another
slightly larger set of non-nutritive vessels is probably interspersed within connective
tissue of the septa and tendons. The fluctuation of flow between these two circuits
allows sensitive control of nutrient delivery, which is often independent of changes in
total flow. These innate flow patterns can be manipulated in vitro by the infusion of
vasoactive agents into the perfused rat hindlimb. Certain vasoconstrictors (including
serotonin) increase connective tissue flow at the expense of muscle capillary flow,
denying access of glucose and insulin to the myocytes and inducing acute insulin
resistance. In vivo, insulin itself causes increased flow to the muscle capillaries, and this
insulin-mediated capillary recruitment is often blocked in insulin resistant states.
This thesis primarily investigates the uptake of blood-borne metabolites during serotonin
infusion in the perfused rat hindlimb, including glucose, fatty acids (FFA, both albuminbound
and derived from chylomicron-triglyceride) and amino acids. In addition, the
effect of elevated plasma FFA on the action of insulin to recruit capillaries was
investigated in the euglycaemic, hyperinsulinaemic clamp in vivo, from the metabolism
of 1-methyl xanthine.
When the ratio of non-nutritive to nutritive flow was increased in the perfused rat
hindlimb, the insulin-mediated uptake of glucose, Na-palmitate (albumin-bound) and aaminoisobutyric
acid were reduced. Unlike the other fuels tested, with high non-nutritive
flow the uptake of FFA from chylomicron-triglyceride hydrolysis was increased. It was
therefore reasoned that non-nutritive flow was accessing a population of adipocytes
within the muscle connective tissue, most likely in the perimysium. This perimysial
adipose tissue is responsible for muscle 'marbling'.
In the experiments determining the effect of FFA on insulin-mediated glucose uptake in
vivo, FFA inhibited both insulin-mediated capillary recruitment and glucose uptake, thus
elevated FFA in vivo were able to induce a state of insulin resistance, likely to be partly
mediated by reduced capillary recruitment or nutritive flow. Accordingly, elevated FFA
prevent perfusion of the nutritive capillaries to some degree, resulting in predominantly
non-nutritive flow. This likely results in the reduced access and uptake of insulin,
glucose, amino acids and albumin-bound fatty acids by myocytes, contributing to their
buildup in the plasma. However, increased flow through the non-nutritive vessels of the
muscle connective tissue, increased the exposure of lipoproteins to lipolytic enzymes.
Thus, non-nutritive flow probably nourishes connective tissue adipocytes and increases
the potential for fat accretion within the muscle.
The results within this thesis offer important insights into nutrient access in skeletal
muscle, in particular with elevated FFA in vivo. A reduction in nutritive flow, caused by
elevated plasma FFA, is likely to reduce the uptake of glucose, amino acids and FFA
into the myocytes, however increase fat deposition in the muscle connective tissue. This
may contribute to the reduction in oxidative capacity, and accelerated 'marbling' and
insulin resistance of human muscle,

Item Type: Thesis - PhD
Authors/Creators:Clerk, Lucy Henrietta
Keywords: Blood flow, Muscles, Vasoconstrictors, Muscles, Metabolites
Copyright Holders: The Author
Copyright Information:

Copyright 2001 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, 2002. Includes bibliographical references

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