Effects of beta cell granule components on human islet amyloid polypeptide fibril formation

FEBS Letters
P WestermarkD F Steiner

Abstract

Formation of amyloid-like fibrils in a solution of human islet amyloid polypeptide (hIAPP) with and without the presence of other beta-cell granule components was studied in vitro. Insulin at less than equimolar concentration strongly inhibited hIAPP fibrillogenesis. Proinsulin had a weaker inhibitory effect while C-peptide, Ca2+ and Zn2+ each individually enhanced fibril formation. C-peptide combined with Ca2+ had an inhibitory effect. Since IAPP was found almost exclusively in the halo fractions of isolated islet secretory granules, primarily the concentrations of C-peptide, Ca2+ and possibly proinsulin may be crucial for the native state of IAPP. It is concluded that an imbalance between fibril formation enhancers and inhibitors may be of importance in the pathogenesis of amyloid in the islets of Langerhans.

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Citations

Jun 3, 2005·Current Diabetes Reports·Per WestermarkGunilla T Westermark
Jul 6, 2012·Current Diabetes Reports·Michael R Rickels
Dec 9, 2003·Journal of Molecular Biology·Jennifer L Larson, Andrew D Miranker
Nov 15, 2002·Molecular and Cellular Endocrinology·T D O'Brien
Dec 19, 2008·The New England Journal of Medicine·Michael R RickelsAli Naji
Apr 15, 2008·Proceedings of the National Academy of Sciences of the United States of America·Maarten F M EngelJo W M Höppener
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Rodolfo Guardado-MendozaFranco Folli
Jun 29, 2006·ILAR Journal·Michael S Henson, Timothy D O'Brien
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Jun 21, 2008·Experimental Diabetes Research·Sharon Gilead, Ehud Gazit
Aug 26, 2011·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Kamille Smidt, Jørgen Rungby
Feb 6, 2013·FEBS Letters·Ping CaoDaniel P Raleigh
May 29, 2009·Protein Science : a Publication of the Protein Society·Jed J W WiltziusDavid Eisenberg
Oct 31, 2012·The FEBS Journal·Michael LandrehHans Jörnvall
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Feb 5, 2008·Biochemical and Biophysical Research Communications·Peng LeiYan-mei Li
Nov 24, 2005·The FEBS Journal·Per Westermark
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Sep 28, 2012·The Biochemical Journal·Michael LandrehHans Jörnvall
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Jan 1, 2008·Experimental Diabetes Research·Arne AnderssonPer Westermark
Jan 28, 2012·Biochemical and Biophysical Research Communications·Michael LandrehHans Jörnvall

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