Advertisement

 

 

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

Zn2+ chelation by serum albumin improves hexameric Zn2+-insulin dissociation into monomers after exocytosis.
Author Information (click to view)

Pertusa JAG, León-Quinto T, Berná G, Tejedo JR, Hmadcha A, Bedoya FJ, Martín F, Soria B,


Pertusa JAG, León-Quinto T, Berná G, Tejedo JR, Hmadcha A, Bedoya FJ, Martín F, Soria B, (click to view)

Pertusa JAG, León-Quinto T, Berná G, Tejedo JR, Hmadcha A, Bedoya FJ, Martín F, Soria B,

Advertisement

PloS one 2017 11 0312(11) e0187547 doi 10.1371/journal.pone.0187547
Abstract

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

2 × 2 =

[ HIDE/SHOW ]