| Zn(II) ions co-secreted with insulin suppress inherent amyloidogenic properties of monomeric insulin. | |
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MedLine Citation:
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PMID: 20632994 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Insulin, a 51-residue peptide hormone, is an intrinsically amyloidogenic peptide, forming amyloid fibrils in vitro. In the secretory granules, insulin is densely packed together with Zn(II) into crystals of Zn(2)Insulin(6) hexamer, which assures osmotic stability of vesicles and prevents fibrillation of the peptide. However, after release from the pancreatic beta-cells, insulin dissociates into active monomers, which tend to fibrillize not only at acidic, but also at physiological, pH values. The effect of co-secreted Zn(II) ions on the fibrillation of monomeric insulin is unknown, however, it might prevent insulin fibrillation. We showed that Zn(II) inhibits fibrillation of monomeric insulin at physiological pH values by forming a soluble Zn(II)-insulin complex. The inhibitory effect of Zn(II) ions is very strong at pH 7.3 (IC(50)=3.5 microM), whereas at pH 5.5 it progressively weakens, pointing towards participation of the histidine residue(s) in complex formation. The results obtained indicate that Zn(II) ions might suppress fibrillation of insulin at its release sites and in circulation. It is hypothesized that misfolded oligomeric intermediates occurring in the insulin fibrillation pathway, especially in zinc-deficient conditions, might induce autoantibodies against insulin, which leads to beta-cell damage and autoimmune Type 1 diabetes. |
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Authors:
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Andra Noormägi; Julia Gavrilova; Julia Smirnova; Vello Tõugu; Peep Palumaa |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 430 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-27 Completed Date: 2010-10-05 Revised Date: 2011-09-06 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 511-8 Citation Subset: IM |
Affiliation:
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Department of Gene Technology, Tallinn University of Technology, Estonia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Amyloid / chemistry*, metabolism, ultrastructure Hydrogen-Ion Concentration Insulin / chemistry*, metabolism Ions Kinetics Microscopy, Electron, Transmission Organometallic Compounds / chemistry*, metabolism Protein Binding Protein Multimerization Spectrometry, Mass, Electrospray Ionization Temperature Zinc / chemistry*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Amyloid; 0/Ions; 0/Organometallic Compounds; 11061-68-0/Insulin; 7440-66-6/Zinc |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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