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<meta content="Kolka, Cathryn" name="eprints.creators_name" />
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<meta content="Glucose uptake occurs in skeletal muscle under basal conditions, and increases in response to stimuli such as insulin and exercise. Exercise is known to increase blood flow, and it appears that insulin has similar hemodynamic effects, including increased blood flow and capillary recruitment, which can modify the amount of glucose uptake occurring under each condition. Here we study factors affecting both basal and stimulated myocyte glucose uptake, with a particular focus on vasoactive agents.
Insulin stimulates the release of endothelin-1 (ET-1), a potent vasoconstrictor, from endothelial cells in culture. As yet it is unknown whether ET-1 is a type A (causing nutritive perfusion) or a type B (non-nutritive) vasoconstrictor, so here we use the pump-perfused rat hindlimb to characterize the distribution effects of ET-1. We show that ET-1 causes a type A vasoconstriction, stimulating basal metabolism at low doses, while at high doses the distribution of flow changes to become non-nutritive, inhibitory to metabolism. As a general vasodilator prevents both metabolic and hemodynamic effects, the effects on metabolism are due to the redistribution of flow. These redistribution effects are confirmed by the ability of high dose ET-1 to decrease aerobic tension development in the contracting hindlimb, and by the ability of low dose ET-1 to increase the interstitial glucose concentration.
Given this understanding of the effects of ET-1 alone, we can investigate the interactions between ET-1 and insulin. In the perfused rat hindlimb, insulin has not been observed to have any vasodilatory effect, whereas here for the first time insulin appears to have vasodilator-like actions against ET-1 mediated vasoconstriction. Also, the redistribution of flow by ET-1 does not appear to alter the metabolic effect of insulin to cause glucose uptake at either dose of ET-1 used.
Nitric Oxide (NO) is thought to be the mechanism by which insulin causes vasodilation in muscle. A previous study has shown that methacholine (MC), by increasing NO, was able to augment insulin-mediated glucose uptake and capillary recruitment, while other NO donors were unable to do so. Here we show that, at the dose used to increase glucose uptake in the previous study, MC has only a vasodilatory effect, and no direct effect on glucose uptake, in the perfused rat hindlimb. At higher doses, an effect on glucose uptake can be observed. This means that the increase in capillary recruitment by MC was responsible for the elevated insulin-mediated glucose uptake, and there was no direct effect of MC on glucose uptake.
A recent publication suggested that the Na+-D-glucose cotransporter (SGLT1) was essential for insulin-mediated glucose uptake, although not required for basal glucose uptake. The implications of this detract from our proposed role of blood flow redistribution in insulin action. In attempting to reproduce these results in the perfused rat hindlimb we found that SGLT1 is not required for insulin-mediated glucose uptake, and confirmed this using a low sodium buffer, which would also inhibit the transporter. We conclude that SGLT1 is not required for insulin-mediated glucose uptake.
Our results therefore suggest that complex interactions are involved in insulin action, some of which involve hemodynamic actions that are capable of altering insulin-mediated glucose uptake, and others in which insulin itself can limit the action of other vasomodulators, such as ET-1. It is apparent, however that SGLT1 in the endothelium may not be necessary for the metabolic effects of insulin, and that blood flow distribution, or capillary recruitment is therefore of great importance in delivering glucose to myocytes." name="eprints.abstract" />
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<meta content="Glucose uptake occurs in skeletal muscle under basal conditions, and increases in response to stimuli such as insulin and exercise. Exercise is known to increase blood flow, and it appears that insulin has similar hemodynamic effects, including increased blood flow and capillary recruitment, which can modify the amount of glucose uptake occurring under each condition. Here we study factors affecting both basal and stimulated myocyte glucose uptake, with a particular focus on vasoactive agents.
Insulin stimulates the release of endothelin-1 (ET-1), a potent vasoconstrictor, from endothelial cells in culture. As yet it is unknown whether ET-1 is a type A (causing nutritive perfusion) or a type B (non-nutritive) vasoconstrictor, so here we use the pump-perfused rat hindlimb to characterize the distribution effects of ET-1. We show that ET-1 causes a type A vasoconstriction, stimulating basal metabolism at low doses, while at high doses the distribution of flow changes to become non-nutritive, inhibitory to metabolism. As a general vasodilator prevents both metabolic and hemodynamic effects, the effects on metabolism are due to the redistribution of flow. These redistribution effects are confirmed by the ability of high dose ET-1 to decrease aerobic tension development in the contracting hindlimb, and by the ability of low dose ET-1 to increase the interstitial glucose concentration.
Given this understanding of the effects of ET-1 alone, we can investigate the interactions between ET-1 and insulin. In the perfused rat hindlimb, insulin has not been observed to have any vasodilatory effect, whereas here for the first time insulin appears to have vasodilator-like actions against ET-1 mediated vasoconstriction. Also, the redistribution of flow by ET-1 does not appear to alter the metabolic effect of insulin to cause glucose uptake at either dose of ET-1 used.
Nitric Oxide (NO) is thought to be the mechanism by which insulin causes vasodilation in muscle. A previous study has shown that methacholine (MC), by increasing NO, was able to augment insulin-mediated glucose uptake and capillary recruitment, while other NO donors were unable to do so. Here we show that, at the dose used to increase glucose uptake in the previous study, MC has only a vasodilatory effect, and no direct effect on glucose uptake, in the perfused rat hindlimb. At higher doses, an effect on glucose uptake can be observed. This means that the increase in capillary recruitment by MC was responsible for the elevated insulin-mediated glucose uptake, and there was no direct effect of MC on glucose uptake.
A recent publication suggested that the Na+-D-glucose cotransporter (SGLT1) was essential for insulin-mediated glucose uptake, although not required for basal glucose uptake. The implications of this detract from our proposed role of blood flow redistribution in insulin action. In attempting to reproduce these results in the perfused rat hindlimb we found that SGLT1 is not required for insulin-mediated glucose uptake, and confirmed this using a low sodium buffer, which would also inhibit the transporter. We conclude that SGLT1 is not required for insulin-mediated glucose uptake.
Our results therefore suggest that complex interactions are involved in insulin action, some of which involve hemodynamic actions that are capable of altering insulin-mediated glucose uptake, and others in which insulin itself can limit the action of other vasomodulators, such as ET-1. It is apparent, however that SGLT1 in the endothelium may not be necessary for the metabolic effects of insulin, and that blood flow distribution, or capillary recruitment is therefore of great importance in delivering glucose to myocytes." name="DC.description" />
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<h1 class="ep_tm_pagetitle">Glucose uptake in skeletal muscle</h1>
<p style="margin-bottom: 1em" class="not_ep_block"><span class="person_name">Kolka, Cathryn</span> (2006) <xhtml:em>Glucose uptake in skeletal muscle.</xhtml:em> PhD thesis, University of Tasmania.</p><p style="margin-bottom: 1em" class="not_ep_block"></p><table style="margin-bottom: 1em" class="not_ep_block"><tr><td valign="top" style="text-align:center"><a onmouseover="EPJS_ShowPreview( event, 'doc_preview_2044' );" href="http://eprints.utas.edu.au/1577/1/KolkaFront.pdf" onmouseout="EPJS_HidePreview( event, 'doc_preview_2044' );"><img alt="[img]" src="http://eprints.utas.edu.au/style/images/fileicons/application_pdf.png" class="ep_doc_icon" border="0" /></a><div class="ep_preview" id="doc_preview_2044"><table><tr><td><img alt="" src="http://eprints.utas.edu.au/1577/thumbnails/1/preview.png" class="ep_preview_image" border="0" /><div class="ep_preview_title">Preview</div></td></tr></table></div></td><td valign="top"><a href="http://eprints.utas.edu.au/1577/1/KolkaFront.pdf"><span class="ep_document_citation">PDF (Front Matter)</span></a> - Requires a PDF viewer<br />54Kb</td></tr><tr><td valign="top" style="text-align:center"><a onmouseover="EPJS_ShowPreview( event, 'doc_preview_2045' );" href="http://eprints.utas.edu.au/1577/2/KolkaWhole.pdf" onmouseout="EPJS_HidePreview( event, 'doc_preview_2045' );"><img alt="[img]" src="http://eprints.utas.edu.au/style/images/fileicons/application_pdf.png" class="ep_doc_icon" border="0" /></a><div class="ep_preview" id="doc_preview_2045"><table><tr><td><img alt="" src="http://eprints.utas.edu.au/1577/thumbnails/2/preview.png" class="ep_preview_image" border="0" /><div class="ep_preview_title">Preview</div></td></tr></table></div></td><td valign="top"><a href="http://eprints.utas.edu.au/1577/2/KolkaWhole.pdf"><span class="ep_document_citation">PDF (Whole Thesis)</span></a> - Requires a PDF viewer<br />909Kb</td></tr></table><div class="not_ep_block"><h2>Abstract</h2><p style="padding-bottom: 16px; text-align: left; margin: 1em auto 0em auto">Glucose uptake occurs in skeletal muscle under basal conditions, and increases in response to stimuli such as insulin and exercise. Exercise is known to increase blood flow, and it appears that insulin has similar hemodynamic effects, including increased blood flow and capillary recruitment, which can modify the amount of glucose uptake occurring under each condition. Here we study factors affecting both basal and stimulated myocyte glucose uptake, with a particular focus on vasoactive agents.
Insulin stimulates the release of endothelin-1 (ET-1), a potent vasoconstrictor, from endothelial cells in culture. As yet it is unknown whether ET-1 is a type A (causing nutritive perfusion) or a type B (non-nutritive) vasoconstrictor, so here we use the pump-perfused rat hindlimb to characterize the distribution effects of ET-1. We show that ET-1 causes a type A vasoconstriction, stimulating basal metabolism at low doses, while at high doses the distribution of flow changes to become non-nutritive, inhibitory to metabolism. As a general vasodilator prevents both metabolic and hemodynamic effects, the effects on metabolism are due to the redistribution of flow. These redistribution effects are confirmed by the ability of high dose ET-1 to decrease aerobic tension development in the contracting hindlimb, and by the ability of low dose ET-1 to increase the interstitial glucose concentration.
Given this understanding of the effects of ET-1 alone, we can investigate the interactions between ET-1 and insulin. In the perfused rat hindlimb, insulin has not been observed to have any vasodilatory effect, whereas here for the first time insulin appears to have vasodilator-like actions against ET-1 mediated vasoconstriction. Also, the redistribution of flow by ET-1 does not appear to alter the metabolic effect of insulin to cause glucose uptake at either dose of ET-1 used.
Nitric Oxide (NO) is thought to be the mechanism by which insulin causes vasodilation in muscle. A previous study has shown that methacholine (MC), by increasing NO, was able to augment insulin-mediated glucose uptake and capillary recruitment, while other NO donors were unable to do so. Here we show that, at the dose used to increase glucose uptake in the previous study, MC has only a vasodilatory effect, and no direct effect on glucose uptake, in the perfused rat hindlimb. At higher doses, an effect on glucose uptake can be observed. This means that the increase in capillary recruitment by MC was responsible for the elevated insulin-mediated glucose uptake, and there was no direct effect of MC on glucose uptake.
A recent publication suggested that the Na+-D-glucose cotransporter (SGLT1) was essential for insulin-mediated glucose uptake, although not required for basal glucose uptake. The implications of this detract from our proposed role of blood flow redistribution in insulin action. In attempting to reproduce these results in the perfused rat hindlimb we found that SGLT1 is not required for insulin-mediated glucose uptake, and confirmed this using a low sodium buffer, which would also inhibit the transporter. We conclude that SGLT1 is not required for insulin-mediated glucose uptake.
Our results therefore suggest that complex interactions are involved in insulin action, some of which involve hemodynamic actions that are capable of altering insulin-mediated glucose uptake, and others in which insulin itself can limit the action of other vasomodulators, such as ET-1. It is apparent, however that SGLT1 in the endothelium may not be necessary for the metabolic effects of insulin, and that blood flow distribution, or capillary recruitment is therefore of great importance in delivering glucose to myocytes.</p></div><table style="margin-bottom: 1em" cellpadding="3" class="not_ep_block" border="0"><tr><th valign="top" class="ep_row">Item Type:</th><td valign="top" class="ep_row">Thesis (PhD)</td></tr><tr><th valign="top" class="ep_row">Keywords:</th><td valign="top" class="ep_row">skeletal muscle, glucose uptake</td></tr><tr><th valign="top" class="ep_row">Subjects:</th><td valign="top" class="ep_row"><a href="http://eprints.utas.edu.au/view/subjects/320300.html">320000 Medical and Health Sciences > 320300 Medical Biochemistry and Clinical Chemistry</a><br /><a href="http://eprints.utas.edu.au/view/subjects/320307.html">320000 Medical and Health Sciences > 320300 Medical Biochemistry and Clinical Chemistry > 320307 Medical Biochemistry - Other</a></td></tr><tr><th valign="top" class="ep_row">ID Code:</th><td valign="top" class="ep_row">1577</td></tr><tr><th valign="top" class="ep_row">Deposited By:</th><td valign="top" class="ep_row"><span class="ep_name_citation"><span class="person_name">Ms Sandy von Allmen</span></span></td></tr><tr><th valign="top" class="ep_row">Deposited On:</th><td valign="top" class="ep_row">09 Aug 2007</td></tr><tr><th valign="top" class="ep_row">Last Modified:</th><td valign="top" class="ep_row">09 Jan 2008 02:30</td></tr><tr><th valign="top" class="ep_row">ePrint Statistics:</th><td valign="top" class="ep_row"><a target="ePrintStats" href="/es/index.php?action=show_detail_eprint;id=1577;">View statistics for this ePrint</a></td></tr></table><p align="right">Repository Staff Only: <a href="http://eprints.utas.edu.au/cgi/users/home?screen=EPrint::View&eprintid=1577">item control page</a></p>
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