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Zn.sup.2+ chelation by serum albumin improves hexameric Zn.sup.2+-insulin dissociation into monomers after exocytosis
[beta]-cells release hexameric Zn.sup.2+ -insulin into the extracellular space, but monomeric Zn.sup.2+ -free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn.sup.2+ concentration-dependent. In th...
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Published in: | PloS one 2017-11, Vol.12 (11), p.e0187547 |
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creator | Pertusa, José A. G León-Quinto, Trinidad Berná, Genoveva Tejedo, Juan R Hmadcha, Abdelkrim Bedoya, Francisco J Martín, Franz Soria, Bernat |
description | [beta]-cells release hexameric Zn.sup.2+ -insulin into the extracellular space, but monomeric Zn.sup.2+ -free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn.sup.2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn.sup.2+ on Zn.sup.2+ -insulin dissociation into Zn.sup.2+ -free insulin and its physiological, methodological and therapeutic relevance. Glucose and K.sup.+ -induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn.sup.2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn.sup.2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn.sup.2+ -free insulin but strongly affects RIA measurements of Zn.sup.2+ -insulin. In contrast, accurate determination of Zn.sup.2+ -insulin was obtained only when bovine serum albumin or Zn.sup.2+ chelators were present in the assay buffer solution. Albumin and Zn.sup.2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn.sup.2+ chelators promotes the conversion of "slow" Zn.sup.2+ -insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn.sup.2+ chelators. These observations support the notion that the Zn.sup.2+ -binding properties of albumin improve the dissociation of Zn.sup.2+ -insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation. |
doi_str_mv | 10.1371/journal.pone.0187547 |
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G ; León-Quinto, Trinidad ; Berná, Genoveva ; Tejedo, Juan R ; Hmadcha, Abdelkrim ; Bedoya, Francisco J ; Martín, Franz ; Soria, Bernat</creator><creatorcontrib>Pertusa, José A. G ; León-Quinto, Trinidad ; Berná, Genoveva ; Tejedo, Juan R ; Hmadcha, Abdelkrim ; Bedoya, Francisco J ; Martín, Franz ; Soria, Bernat</creatorcontrib><description>[beta]-cells release hexameric Zn.sup.2+ -insulin into the extracellular space, but monomeric Zn.sup.2+ -free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn.sup.2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn.sup.2+ on Zn.sup.2+ -insulin dissociation into Zn.sup.2+ -free insulin and its physiological, methodological and therapeutic relevance. Glucose and K.sup.+ -induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn.sup.2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn.sup.2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn.sup.2+ -free insulin but strongly affects RIA measurements of Zn.sup.2+ -insulin. In contrast, accurate determination of Zn.sup.2+ -insulin was obtained only when bovine serum albumin or Zn.sup.2+ chelators were present in the assay buffer solution. Albumin and Zn.sup.2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn.sup.2+ chelators promotes the conversion of "slow" Zn.sup.2+ -insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn.sup.2+ chelators. These observations support the notion that the Zn.sup.2+ -binding properties of albumin improve the dissociation of Zn.sup.2+ -insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0187547</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Albumin ; Analysis ; Exocytosis ; Health aspects ; Insulin ; Physiological aspects</subject><ispartof>PloS one, 2017-11, Vol.12 (11), p.e0187547</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Pertusa, José A. G</creatorcontrib><creatorcontrib>León-Quinto, Trinidad</creatorcontrib><creatorcontrib>Berná, Genoveva</creatorcontrib><creatorcontrib>Tejedo, Juan R</creatorcontrib><creatorcontrib>Hmadcha, Abdelkrim</creatorcontrib><creatorcontrib>Bedoya, Francisco J</creatorcontrib><creatorcontrib>Martín, Franz</creatorcontrib><creatorcontrib>Soria, Bernat</creatorcontrib><title>Zn.sup.2+ chelation by serum albumin improves hexameric Zn.sup.2+-insulin dissociation into monomers after exocytosis</title><title>PloS one</title><description>[beta]-cells release hexameric Zn.sup.2+ -insulin into the extracellular space, but monomeric Zn.sup.2+ -free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn.sup.2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn.sup.2+ on Zn.sup.2+ -insulin dissociation into Zn.sup.2+ -free insulin and its physiological, methodological and therapeutic relevance. Glucose and K.sup.+ -induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn.sup.2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn.sup.2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn.sup.2+ -free insulin but strongly affects RIA measurements of Zn.sup.2+ -insulin. In contrast, accurate determination of Zn.sup.2+ -insulin was obtained only when bovine serum albumin or Zn.sup.2+ chelators were present in the assay buffer solution. Albumin and Zn.sup.2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn.sup.2+ chelators promotes the conversion of "slow" Zn.sup.2+ -insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn.sup.2+ chelators. These observations support the notion that the Zn.sup.2+ -binding properties of albumin improve the dissociation of Zn.sup.2+ -insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.</description><subject>Albumin</subject><subject>Analysis</subject><subject>Exocytosis</subject><subject>Health aspects</subject><subject>Insulin</subject><subject>Physiological aspects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqN0E1Lw0AQBuAgCtbqP_CwIAgiibvZZLM9luJHoVDw6-ClbDaTZkuyWzIbaf-9kYq04EHmMMPwvHOYILhkNGI8Y3cr17VW1dHaWYgok1maZEfBgI14HIqY8uO9-TQ4Q1xRmnIpxCDoPmyE3TqKb4muoFbeOEvyLUFou4aoOu8aY4lp1q37BCQVbFQDrdHkNxcai13do8IgOm12J4z1jjTOul4jUaWHlsDG6a13aPA8OClVjXDx04fB28P96-QpnM0fp5PxLFwyIWgY0zgpR0zlkkomuUpYRgVPyzSDjKt0VMhCCshyYBqgpAmXcQJCQsHTPOdpzIfB1e7uUtWwMLZ0vlW6MagX45Rxlkgpaa-iP1RfBTRG9z8tTb8_CNwcBHrjYeOXqkNcTF-e_2_n74f2es9WoGpfoau774_iPvwCQymZRA</recordid><startdate>20171103</startdate><enddate>20171103</enddate><creator>Pertusa, José A. G</creator><creator>León-Quinto, Trinidad</creator><creator>Berná, Genoveva</creator><creator>Tejedo, Juan R</creator><creator>Hmadcha, Abdelkrim</creator><creator>Bedoya, Francisco J</creator><creator>Martín, Franz</creator><creator>Soria, Bernat</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20171103</creationdate><title>Zn.sup.2+ chelation by serum albumin improves hexameric Zn.sup.2+-insulin dissociation into monomers after exocytosis</title><author>Pertusa, José A. G ; León-Quinto, Trinidad ; Berná, Genoveva ; Tejedo, Juan R ; Hmadcha, Abdelkrim ; Bedoya, Francisco J ; Martín, Franz ; Soria, Bernat</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g1660-2024f91ab808183a4170635f57e73a59d8d86e7be1ceef043824e68ed35bb3523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Albumin</topic><topic>Analysis</topic><topic>Exocytosis</topic><topic>Health aspects</topic><topic>Insulin</topic><topic>Physiological aspects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pertusa, José A. G</creatorcontrib><creatorcontrib>León-Quinto, Trinidad</creatorcontrib><creatorcontrib>Berná, Genoveva</creatorcontrib><creatorcontrib>Tejedo, Juan R</creatorcontrib><creatorcontrib>Hmadcha, Abdelkrim</creatorcontrib><creatorcontrib>Bedoya, Francisco J</creatorcontrib><creatorcontrib>Martín, Franz</creatorcontrib><creatorcontrib>Soria, Bernat</creatorcontrib><collection>Gale in Context : Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pertusa, José A. G</au><au>León-Quinto, Trinidad</au><au>Berná, Genoveva</au><au>Tejedo, Juan R</au><au>Hmadcha, Abdelkrim</au><au>Bedoya, Francisco J</au><au>Martín, Franz</au><au>Soria, Bernat</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Zn.sup.2+ chelation by serum albumin improves hexameric Zn.sup.2+-insulin dissociation into monomers after exocytosis</atitle><jtitle>PloS one</jtitle><date>2017-11-03</date><risdate>2017</risdate><volume>12</volume><issue>11</issue><spage>e0187547</spage><pages>e0187547-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>[beta]-cells release hexameric Zn.sup.2+ -insulin into the extracellular space, but monomeric Zn.sup.2+ -free insulin appears to be the only biologically active form. The mechanisms implicated in dissociation of the hexamer remain unclear, but they seem to be Zn.sup.2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn.sup.2+ on Zn.sup.2+ -insulin dissociation into Zn.sup.2+ -free insulin and its physiological, methodological and therapeutic relevance. Glucose and K.sup.+ -induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn.sup.2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn.sup.2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn.sup.2+ -free insulin but strongly affects RIA measurements of Zn.sup.2+ -insulin. In contrast, accurate determination of Zn.sup.2+ -insulin was obtained only when bovine serum albumin or Zn.sup.2+ chelators were present in the assay buffer solution. Albumin and Zn.sup.2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn.sup.2+ chelators promotes the conversion of "slow" Zn.sup.2+ -insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn.sup.2+ chelators. These observations support the notion that the Zn.sup.2+ -binding properties of albumin improve the dissociation of Zn.sup.2+ -insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0187547</doi><tpages>e0187547</tpages></addata></record> |
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subjects | Albumin Analysis Exocytosis Health aspects Insulin Physiological aspects |
title | Zn.sup.2+ chelation by serum albumin improves hexameric Zn.sup.2+-insulin dissociation into monomers after exocytosis |
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