This study shows for the first time that pharmacologically increase blood flow and perfusion of muscle during hyperinsulinemia
in the elderly increases protein synthesis and muscle insulin resistance overcomes the age anabolism of proteins. In particular, local infusion of sodium nitroprusside during hyperinsulinemia in our older subjects more than twice as common >> << leg blood flow, as planned, and raised nine times increase in muscle perfusion microvessels, thereby increasing amino
delivery to the muscles and stimulates muscle protein synthesis to levels comparable to those observed during infusion of insulin
Only in young healthy people (
). Conversely, when insulin was introduced only in the control group, it induced no vessels, no increase in amino acid
delivery to the leg. In addition, muscle protein synthesis is increased, confirming previous reports from our group and others >> << that physiological vasodilator and muscle protein anabolic effect of insulin observed in young healthy subjects >> << , is lost with age (,
). These data provide convincing evidence that the ability of insulin to stimulate blood circulation and delivery of amino acids necessary >> << to cause muscle protein synthetic response. This interpretation is confirmed further our recently found that pharmacological blockade
insulin-induced vasodilation eliminates the anabolic response of muscle insulin infusion in young subjects
(
). Interestingly, phenylalanine release from muscle protein breakdown, rather than foot speed emergence, increased in the group passes >> << pharmacological vasodilation, albeit to a lesser extent than protein synthesis. As a result, phenylalanine net balance between
foot switches from negative to positive, indicating a net gain of muscle protein in the SNP group at >> hyperinsulinemia. << This is a significant positive effect on vasodilation net balance shows that the increase in muscle protein decay
was not due to artifact or model leaching effect induced blood flow expansion, as in cases
balance remains negative. Instead, significant changes in muscle protein breakdown is due to the acceleration >> << intracellular protein metabolism, as evidenced by a significant increase in intracellular processing of phenylalanine breakdown >> << to the synthesis . Increasing the concentration of amino acid treatment also occurs in young subjects in isolated
physiological hyperinsulinemia, while the availability of amino acids is reduced (,
). This may partly explain the conflicting results in the literature the effect of insulin on protein synthesis and breakdown of
. For example, unlike the data from our laboratory (,,,,
) and others (,,
BЂ "), hyperinsulinemia, reportedly has no effect on muscle protein synthesis, but also prevent muscle protein breakdown
(
BЂ "). We believe that this discrepancy may be due to differences in availability of amino acids. In studies reporting insulin
increase muscle protein synthesis (,,,,,,,,
), delivery of amino acids increased by exogenous or infusion or increased blood flow without changing the amino acid concentration
as in this study. On the other hand, studies show no increase in the synthesis of reduced breakdown also reported decreased or unchanged
, availability of amino acids (,,,
), mainly due to significant decrease in blood concentrations of amino acid-induced systemic hyperinsulinemia. Blood flowBЂ "and, more importantly, muscle perfusionBЂ" serve as an important contribution to the anabolic effect of insulin on muscle protein
age and insulin resistance of muscle protein metabolism. Enhanced perfusion of microvessels increased insulin
delivery to muscles and tissues of the influence of insulin. Insulin has been reported to promote its own transport
through endothelial barrier to provide its receptor on the ultimate goal of tissue such as skeletal muscle, and this process can be
nasyschayutsya (
). During this process, and insulin increases microvascular surface to absorb through the capillary endothelial dependent on set
(,
), thus contributing to its delivery to skeletal muscle. This mechanism can probably be lost in older subjects because of >> << to endothelial dysfunction and inability to hire capillaries (,
). Thus, the recovery vessels and capillary recruitment during hyperinsulinemia in our old subjects could lead to
observed improvement in muscle insulin resistance age protein metabolism by increasing the number of muscle insulin effects >> << . This explanation is confirmed by increased Akt / PKB phosphorylation in SNP group compared with control group
during hyperinsulinemia. Enhanced Akt / PKB phosphorylation, however, does not lead to further >> << increase glucose SNP group was slightly lower, although not significantly, than in the control group due to the release of
. For a modest improvement Akt / PKB phosphorylation may have been insufficient to activate the signals further downstream
in the way glucose is not measured in this study, or glucose, may have been built >> << In these two groups of healthy, diabetes subjects. It would not be surprising, as we have shown that glucose metabolism
insulin more sensitive than protein metabolism in healthy subjects without diabetes (
), and that the age of insulin resistance in muscle metabolism proteins does not correlate with
insulin sensitivity of glucose metabolism (
). However, this explanation is unlikely to be used in our experiment because we used a physiological dose of insulin
insufficient to maximally stimulate glucose absorption. Recently the theory (
) provides, in essence, that increased perfusion only increases the maximum absorption of glucose, when large gradients arteriovenous glucose
happen. On the contrary, compared with glucose, amino acids present in blood in very low concentrations and with a large
arteriovenous gradients. Thus, their use may be more sensitive to changes in blood flow. Finally, it is also possible that we missed
differences in glucose due to the schedule of blood sampling. Large SNP-induced increase in blood flow and microvascular perfusion reduced amino acid transport in muscle. But
MTOR phosphorylation of 2448 Ser, which usually responds to changes in the availability of amino acids (
), increased significantly in both groups the same extent as during hyperinsulinemia. Recently it was reported that elevated levels of nitric oxide
MTOR inhibit signaling (
). Because sodium nitroprusside is a direct donor of nitric oxide, nitric oxide excess of sodium nitroprusside infusion
may have blunted activation MTOR in response to increased delivery of amino acids in a group of SNP. However, the lack of >> << group differences in activation of signaling pathway MTOR obviously does not prevent an increase in muscle protein synthesis in the group
SNP. How MTOR, S6K1 and 4E-BP1 lasix 30 mg is equally high in both groups during hyperinsulinemia, >> << protein kinetics observed differences between the SNP and control objects may be due to the already active translational >> << techniques yielding more amino acids in a group of SNP. This interpretation is confirmed by preliminary data that amino acids, free
and transport in muscle appears to modulate the action of insulin on muscle protein synthesis and destruction
(,,,,
). Finally, we can not exclude the possibility that our muscles sampling schedule, while adequate for detecting changes in protein turnover >> << was not timed to capture the changes in intracellular signaling in these experimental conditions . Overall, these findings suggest that pharmacological restoration of nitric oxide vasodilation during hyperinsulinemia
can restore physiological anabolic response of skeletal muscle proteins to insulin in elderly people. This effect is
Mediation increase the availability of amino acids in skeletal muscle during hyperinsulinemia conditions. Further studies in
study the effect of isolated blood vessels in muscle protein turnover, it is necessary to clarify this point. The results of this survey >> << are encouraging first step for future research the possibility of using pharmacological agents for treatment >> << sarkopeniyi in older people, especially those whose physical limitations prevent interference with lifestyle, such as exercise (
BЂ ") is known to improve muscle function and metabolism. .
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