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Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus
Journal of Pharmaceutical Analysis ( IF 6.1 ) Pub Date : 2022-04-07 , DOI: 10.1016/j.jpha.2022.04.001
Pratiksha H Roham 1 , Shreyada N Save 1 , Shilpy Sharma 1
Affiliation  

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 β-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 β-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.



中文翻译:

人胰岛淀粉样多肽:治疗 2 型糖尿病的治疗靶点

由于缺乏合适的预后和诊断标志物,2 型糖尿病 (T2DM) 和其他代谢紊乱通常不会在患者中引起注意和忽视。目前可用于管理 T2DM 的治疗方案不能逆转糖尿病;相反,它们延缓了糖尿病的进展。如果在早期阶段实施,它们的功效(原则上)可能会显着提高。人胰岛淀粉样多肽 (hIAPP) 或胰淀素的错误折叠和聚集与 T2DM 患者胰腺 β 细胞功能和质量的逐渐下降有关。因此,hIAPP 已被公认为治疗 T2DM 的治疗靶点。本综述总结了 hIAPP 通过诱导内质网应激、氧化应激、线粒体功能障碍、炎性细胞因子分泌、自噬阻断等。此外,它探索了使用 hIAPP 聚集途径的中间体作为 T2DM 管理的潜在药物靶点的可能性。最后,常见抗糖尿病分子和再利用药物的作用;其他 hIAPP 模拟物和肽;有机小分子和天然化合物;纳米粒子、纳米体和量子点;金属和金属络合物;已经证明有潜力抑制和/或逆转 hIAPP 聚集并因此可以进一步开发用于管理 T2DM 的伴侣蛋白和伴侣蛋白已被讨论。常见抗糖尿病分子和重新利用药物的作用;其他 hIAPP 模拟物和肽;有机小分子和天然化合物;纳米粒子、纳米体和量子点;金属和金属络合物;已经证明有潜力抑制和/或逆转 hIAPP 聚集并因此可以进一步开发用于管理 T2DM 的伴侣蛋白和伴侣蛋白已被讨论。常见抗糖尿病分子和重新利用药物的作用;其他 hIAPP 模拟物和肽;有机小分子和天然化合物;纳米粒子、纳米体和量子点;金属和金属络合物;已经证明有潜力抑制和/或逆转 hIAPP 聚集并因此可以进一步开发用于管理 T2DM 的伴侣蛋白和伴侣蛋白已被讨论。

更新日期:2022-04-07
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