Blockade of islet amyloid polypeptide fibrillation and cytotoxicity by the secretory chaperones 7B2 and proSAAS

FEBS Lett. 2013 Nov 1;587(21):3406-11. doi: 10.1016/j.febslet.2013.09.006. Epub 2013 Sep 13.


The deposition of fibrillated human islet β-cell peptide islet amyloid polypeptide (hIAPP) into amyloid plaques is characteristic of the pathogenesis of islet cell death during type 2 diabetes. We investigated the effects of the neuroendocrine secretory proteins 7B2 and proSAAS on hIAPP fibrillation in vitro and on cytotoxicity. In vitro, 21-kDa 7B2 and proSAAS blocked hIAPP fibrillation. Structure-function studies showed that a central region within 21-kDa 7B2 is important in this effect and revealed the importance of the N-terminal region of proSAAS. Both chaperones blocked the cytotoxic effects of exogenous hIAPP on Rin5f cells; 7B2 generated by overexpression was also effective. ProSAAS and 7B2 may perform a chaperone role as secretory anti-aggregants in normal islet cell function and in type 2 diabetes.

Keywords: 7B2; AD; Alzheimer’s disease; BSA; CA; FBS; IAPP; PBS; PC1/3; PD; Parkinson’s disease; T2DM; TBS; ThT; Type 2 diabetes; bovine serum albumin; carbonic anhydrase; fetal bovine serum; hIAPP; islet amyloid polypeptide; phosphate–buffered saline; proSAAS; prohormone convertase 1/3; thioflavin T; tris–buffered saline; type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Humans
  • Islet Amyloid Polypeptide / antagonists & inhibitors*
  • Islet Amyloid Polypeptide / metabolism
  • Islet Amyloid Polypeptide / toxicity*
  • Mice
  • Molecular Chaperones / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Neuroendocrine Secretory Protein 7B2 / metabolism*
  • Neuropeptides
  • Rats


  • Islet Amyloid Polypeptide
  • Molecular Chaperones
  • Nerve Tissue Proteins
  • Neuroendocrine Secretory Protein 7B2
  • Neuropeptides
  • Pcsk1n protein, mouse
  • SCG5 protein, human