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Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells
Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchab...
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Published in: | PloS one 2013-03, Vol.8 (3), p.e57559 |
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description | Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis. |
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In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0057559</identifier><identifier>PMID: 23520472</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adipocytes - cytology ; Adipocytes - metabolism ; Animals ; Biology ; Cell Membrane Structures - genetics ; Cell Membrane Structures - metabolism ; Cell membranes ; Childrens health ; Clusters ; Collision dynamics ; Confinement ; Diabetes ; Dispersion ; Dissociation ; Elongation ; Endocrinology ; Engineering ; Exocytosis ; Fluorescence ; Glucose ; Glucose - genetics ; Glucose - metabolism ; Glucose transporter ; Glucose Transporter Type 4 - genetics ; Glucose Transporter Type 4 - metabolism ; Homeostasis ; Homeostasis - physiology ; Insulin ; Insulin - metabolism ; Kidney diseases ; Lipids ; Localization ; Male ; Metabolism ; Metabolites ; Microscopy ; Monomers ; Physiological aspects ; Protein Transport - physiology ; Proteins ; Rats ; Rats, Sprague-Dawley ; Regulation ; Transporter</subject><ispartof>PloS one, 2013-03, Vol.8 (3), p.e57559</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c659t-803cdd2d9ebadb2e16f2a8707b821241c576286fa6eab6a4558e0a4015322bfc3</citedby><cites>FETCH-LOGICAL-c659t-803cdd2d9ebadb2e16f2a8707b821241c576286fa6eab6a4558e0a4015322bfc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1330881480/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1330881480?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23520472$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Miele, Claudia</contributor><creatorcontrib>Lizunov, Vladimir A</creatorcontrib><creatorcontrib>Stenkula, Karin</creatorcontrib><creatorcontrib>Troy, Aaron</creatorcontrib><creatorcontrib>Cushman, Samuel W</creatorcontrib><creatorcontrib>Zimmerberg, Joshua</creatorcontrib><title>Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Insulin-stimulated delivery of glucose transporter-4 (GLUT4) to the plasma membrane (PM) is the hallmark of glucose metabolism. In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.</description><subject>Adipocytes - cytology</subject><subject>Adipocytes - metabolism</subject><subject>Animals</subject><subject>Biology</subject><subject>Cell Membrane Structures - genetics</subject><subject>Cell Membrane Structures - metabolism</subject><subject>Cell membranes</subject><subject>Childrens health</subject><subject>Clusters</subject><subject>Collision dynamics</subject><subject>Confinement</subject><subject>Diabetes</subject><subject>Dispersion</subject><subject>Dissociation</subject><subject>Elongation</subject><subject>Endocrinology</subject><subject>Engineering</subject><subject>Exocytosis</subject><subject>Fluorescence</subject><subject>Glucose</subject><subject>Glucose - genetics</subject><subject>Glucose - metabolism</subject><subject>Glucose transporter</subject><subject>Glucose Transporter Type 4 - genetics</subject><subject>Glucose Transporter Type 4 - 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In this study we examined insulin's effects on GLUT4 organization in PM of adipose cells by direct microscopic observation of single monomers tagged with photoswitchable fluorescent protein. In the basal state, after exocytotic delivery only a fraction of GLUT4 is dispersed into the PM as monomers, while most of the GLUT4 stays at the site of fusion and forms elongated clusters (60-240 nm). GLUT4 monomers outside clusters diffuse freely and do not aggregate with other monomers. In contrast, GLUT4 molecule collision with an existing cluster can lead to immediate confinement and association with that cluster. Insulin has three effects: it shifts the fraction of dispersed GLUT4 upon delivery, it augments the dissociation of GLUT4 monomers from clusters ∼3-fold and it decreases the rate of endocytic uptake. All together these three effects of insulin shift most of the PM GLUT4 from clustered to dispersed states. GLUT4 confinement in clusters represents a novel kinetic mechanism for insulin regulation of glucose homeostasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23520472</pmid><doi>10.1371/journal.pone.0057559</doi><tpages>e57559</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adipocytes - cytology Adipocytes - metabolism Animals Biology Cell Membrane Structures - genetics Cell Membrane Structures - metabolism Cell membranes Childrens health Clusters Collision dynamics Confinement Diabetes Dispersion Dissociation Elongation Endocrinology Engineering Exocytosis Fluorescence Glucose Glucose - genetics Glucose - metabolism Glucose transporter Glucose Transporter Type 4 - genetics Glucose Transporter Type 4 - metabolism Homeostasis Homeostasis - physiology Insulin Insulin - metabolism Kidney diseases Lipids Localization Male Metabolism Metabolites Microscopy Monomers Physiological aspects Protein Transport - physiology Proteins Rats Rats, Sprague-Dawley Regulation Transporter |
title | Insulin regulates Glut4 confinement in plasma membrane clusters in adipose cells |
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