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Título

Zn2+ chelation by serum albumin improves hexameric Zn2+ -insulin dissociation into monomers after exocytosis

AutorPertusa, 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 publicación2017
EditorPublic Library of Science
CitaciónPLoS ONE 12(11): e0187547 (2017)
Resumenβ-cells release hexameric Zn-insulin into the extracellular space, but monomeric Zn-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 concentration-dependent. In this study, we investigate the influence of albumin binding to Zn on Zn-insulin dissociation into Zn-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 Zn chelators. Insulin tolerance tests were performed in rats using different insulin solutions with and without Zn and/or albumin. Albumin-free buffer does not alter quantification by RIA of Zn-free insulin but strongly affects RIA measurements of Zn-insulin. In contrast, accurate determination of Zn-insulin was obtained only when bovine serum albumin or Zn chelators were present in the assay buffer solution. Albumin and Zn chelators do not modify insulin release but do affect insulin determination. Preincubation with albumin or Zn chelators promotes the conversion of “slow” Zn-insulin into “fast” insulin. Consequently, insulin diffusion from large islets is ameliorated in the presence of Zn chelators. These observations support the notion that the Zn-binding properties of albumin improve the dissociation of Zn-insulin into subunits after exocytosis, which may be useful in insulin determination, insulin pharmacokinetic assays and islet transplantation.
Versión del editorhttps://doi.org/10.1371/journal.pone.0187547
URIhttp://hdl.handle.net/10261/165410
Identificadoresdoi: 10.1371/journal.pone.0187547
e-issn: 1932-6203
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