Artículo
Zn2+ chelation by serum albumin improves hexameric Zn2+ -insulin dissociation into monomers after exocytosis
Autor/es | Pertusa, José A. G.
León Quinto, Trinidad Berná, Genoveva Tejedo Huamán, Juan Rigoberto Hmadcha, Abdelkrim Bedoya Bergua, Francisco Javier Martín, Franz Soria Escoms, Bernat |
Fecha de publicación | 2017 |
Fecha de depósito | 2018-12-20 |
Publicado en |
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Resumen | 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, ... 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 ªslowº Zn2+-insulin into ªfastº 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. |
Cita | Pertusa, J.A.G., León Quinto, T., Berná, G., Tejedo Huamán, J.R., Hmadcha, A., Bedoya Bergua, F.J.,...,Soria Escoms, B. (2017). Zn2+ chelation by serum albumin improves hexameric Zn2+ -insulin dissociation into monomers after exocytosis. PLoS ONE, 12, 1-16. |
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