Islet amyloid polypeptide(IAPP),or amylin,has been identifi ed as a key factor in the development of type 2 diabetes(T2D).IAPP aggregates,which form amyloid fi brils,contribute to cytotoxicity of the pancreatic β-cel...Islet amyloid polypeptide(IAPP),or amylin,has been identifi ed as a key factor in the development of type 2 diabetes(T2D).IAPP aggregates,which form amyloid fi brils,contribute to cytotoxicity of the pancreatic β-cells,resulting in loss of function and subsequent reduction in insulin production.As a result,surviving β-cells overcompensate for this reduction of insulin production,further contributing to the loss of function because of increased stress,thus leading to insulin resistance.Endogenously,IAPP monomers function in a variety of roles;however,aggregation renders them non-functional.The use of naturally occurring compounds,including peptides and phytochemicals,has been explored as a way to mitigate or inhibit IAPP fi bril formation.This review discusses the structure,endogenous roles and mechanism of IAPP fi bril formation,recent advances on inhibitors of IAPP fi bril formation,and new insights on the future development and application of foodderived inhibitors towards T2D management.展开更多
基金Authors acknowledge the financial support from the Natural Sciences and Engineering Research Council of Canada(NSERC)(grant number RGPIN-2018-06839)the University Research Chairs Program of the University of Ottawa,Canada.
文摘Islet amyloid polypeptide(IAPP),or amylin,has been identifi ed as a key factor in the development of type 2 diabetes(T2D).IAPP aggregates,which form amyloid fi brils,contribute to cytotoxicity of the pancreatic β-cells,resulting in loss of function and subsequent reduction in insulin production.As a result,surviving β-cells overcompensate for this reduction of insulin production,further contributing to the loss of function because of increased stress,thus leading to insulin resistance.Endogenously,IAPP monomers function in a variety of roles;however,aggregation renders them non-functional.The use of naturally occurring compounds,including peptides and phytochemicals,has been explored as a way to mitigate or inhibit IAPP fi bril formation.This review discusses the structure,endogenous roles and mechanism of IAPP fi bril formation,recent advances on inhibitors of IAPP fi bril formation,and new insights on the future development and application of foodderived inhibitors towards T2D management.
