Human islet amyloid polypeptide:A therapeutic target for the management of type 2 diabetes mellitus

作     者：Pratiksha H.Roham Shreyada N.Save Shilpy Sharma Pratiksha H.Roham;Shreyada N.Save;Shilpy Sharma

作者机构：Department of BiotechnologySavitribai Phule Pune UniversityGaneshkhind41100India 

出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)

年 卷 期：2022年第12卷第4期

页      面：556-569页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学] 

基　　金：the Wadhwani Research Foundation(Wadhwani Research Centre for Bioengineering,Grant No.:RD/0118-DONWR04-001) Ramalingaswami Fellowship(Project No.:BT/RLF/Re-entry/11/2012,Department of Biotechnology-DBT,Government of India) University Grants Commission(Grant No.:F.4-5(18-FRP)(IV-Cycle)/2017(BSR),Government of India) generously supported by Research and Development Grant to the Department of Biotechnology,SPPU,and UPE Phase Ⅱ and RUSA 2.0 grants to SPPU CSIR-SRF,GOI(Grant No.:(09/137/0602)2019-EMR-I),for her SRF fellowship Wadhwani Research Foundation(Grant No.:RD/0118-DONWR04-001) RUSA 2.0 grants for her project assistant fellowship. 

主　　题：Aggregation Inhibitor Therapeutic target hIAPP Type 2 diabetes mellitus 

摘      要：Type 2 diabetes mellitus(T2DM)and other metabolic disorders are often silent and go unnoticed in patients because of the lack of suitable prognostic and diagnostic markers.The current therapeutic regimens available for managing T2DM do not reverse diabetes;instead,they delay the progression of diabetes.Their efficacy(in principle)may be significantly improved if implemented at earlier stages.The misfolding and aggregation of human islet amyloid polypeptide(hIAPP)or amylin has been associated with a gradual decrease in pancreatic b-cell function and mass in patients with T2DM.Hence,hIAPP has been recognized as a therapeutic target for managing T2DM.This review summarizes hIAPP s role in mediating dysfunction and apoptosis in pancreatic b-cells via induction of endoplasmic reticulum stress,oxidative stress,mitochondrial dysfunction,inflammatory cytokine secretion,autophagy blockade,etc.Furthermore,it explores the possibility of using intermediates of the hIAPP aggregation pathway as potential drug targets for T2DM management.Finally,the effects of common antidiabetic molecules and repurposed drugs;other hIAPP mimetics and peptides;small organic molecules and natural compounds;nanoparticles,nanobodies,and quantum dots;metals and metal complexes;and chaperones that have demonstrated potential to inhibit and/or reverse hIAPP aggregation and can,therefore,be further developed for managing T2DM have been discussed.