Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis.
β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-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 Zn2+ concentration-dependent. In this study, we investiga...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5669427?pdf=render |
| _version_ | 1828156416762839040 |
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| author | José A G Pertusa Trinidad León-Quinto Genoveva Berná Juan R Tejedo Abdelkrim Hmadcha Francisco J Bedoya Franz Martín Bernat Soria |
| author_facet | José A G Pertusa Trinidad León-Quinto Genoveva Berná Juan R Tejedo Abdelkrim Hmadcha Francisco J Bedoya Franz Martín Bernat Soria |
| author_sort | José A G Pertusa |
| collection | DOAJ |
| description | β-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-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 Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn2+-free insulin but strongly affects RIA measurements of Zn2+-insulin. In contrast, accurate determination of Zn2+-insulin was obtained only when bovine serum albumin or Zn2+ chelators were present in the assay buffer solution. Albumin and Zn2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn2+ chelators promotes the conversion of "slow" Zn2+-insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn2+ chelators. These observations support the notion that the Zn2+-binding properties of albumin improve the dissociation of Zn2+-insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation. |
| first_indexed | 2024-04-11T23:10:40Z |
| format | Article |
| id | doaj.art-34b372d95c234efead5d35e02d86b347 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-11T23:10:40Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-34b372d95c234efead5d35e02d86b3472022-12-22T03:57:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018754710.1371/journal.pone.0187547Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis.José A G PertusaTrinidad León-QuintoGenoveva BernáJuan R TejedoAbdelkrim HmadchaFrancisco J BedoyaFranz MartínBernat Soriaβ-cells release hexameric Zn2+-insulin into the extracellular space, but monomeric Zn2+-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 Zn2+ concentration-dependent. In this study, we investigate the influence of albumin binding to Zn2+ on Zn2+-insulin dissociation into Zn2+-free insulin and its physiological, methodological and therapeutic relevance. Glucose and K+-induced insulin release were analyzed in isolated mouse islets by static incubation and perifusion experiments in the presence and absence of albumin and Zn2+ chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn2+ and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn2+-free insulin but strongly affects RIA measurements of Zn2+-insulin. In contrast, accurate determination of Zn2+-insulin was obtained only when bovine serum albumin or Zn2+ chelators were present in the assay buffer solution. Albumin and Zn2+ chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn2+ chelators promotes the conversion of "slow" Zn2+-insulin into "fast" insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn2+ chelators. These observations support the notion that the Zn2+-binding properties of albumin improve the dissociation of Zn2+-insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.http://europepmc.org/articles/PMC5669427?pdf=render |
| spellingShingle | José A G Pertusa Trinidad León-Quinto Genoveva Berná Juan R Tejedo Abdelkrim Hmadcha Francisco J Bedoya Franz Martín Bernat Soria Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis. PLoS ONE |
| title | Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis. |
| title_full | Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis. |
| title_fullStr | Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis. |
| title_full_unstemmed | Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis. |
| title_short | Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis. |
| title_sort | zn2 chelation by serum albumin improves hexameric zn2 insulin dissociation into monomers after exocytosis |
| url | http://europepmc.org/articles/PMC5669427?pdf=render |
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