Causative factors for formation of toxic islet amyloid polypeptide oligomer in XXXX .

@entity1 @entity2532 @entity527 @entity6 @entity1423 @entity920 @entity1520 @entity16552
@entity1 islet amyloid polypeptide (h- @entity2532 ) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic b-cells. Recently, h- @entity2532 was proposed to be the main component responsible for the cytotoxic pancreatic @entity527 in @entity1 with @entity6 ( @entity6 ). Since the causative factors of @entity2532 (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h- @entity2532 aggregation. Not all forms of @entity2532 aggregates trigger the destruction of b-cell function and loss of b-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in @entity6 , they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic @entity2532 oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the @entity2532 monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence @entity1423 (eg, absence of @entity16552 enzyme, deamidation, reduction of @entity1520 bonds, environmental factors in the cell, genetic mutations, @entity920 metal ions, and heparin) will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to @entity2532 oligomer formation and support studies for investigating novel @entity6 therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of @entity6 pathology.
