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.
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