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

• Published in: Journal of pharmaceutical analysis Vol. 12; no. 4; pp. 556 - 569
• Main Authors: Roham, Pratiksha H., Save, Shreyada N., Sharma, Shilpy
• Format: Journal Article
• Language: English
• Published: Xi'an Elsevier B.V 01.08.2022; Xi'an Jiaotong University, Journal of Pharmaceutical Analysis; Department of Biotechnology,Savitribai Phule Pune University,Ganeshkhind,41100,India; Xi'an Jiaotong University
• Subjects: Aggregation; Alzheimer's disease; Amino acids; Amylin; Amyloid; Apoptosis; Autophagy; Cardiovascular disease; Cytokines; Diabetes; Diabetes mellitus (non-insulin dependent); Drug development; Endoplasmic reticulum; Glucagon; Glucose; hIAPP; Histocompatibility antigen HLA; Hyperglycemia; Inflammation; Inhibitor; Insulin resistance; Intermediates; Metabolic disorders; Metals; Mitochondria; Nanobodies; Nanoparticles; Oxidative stress; Pancreas; Physiology; Polypeptides; Proteins; Quantum dots; Review Paper; Therapeutic applications; Therapeutic target; Therapeutic targets; Type 2 diabetes mellitus; Aggregation; Inhibitor; hIAPP; Type 2 diabetes mellitus; Therapeutic target
• ISSN: 2095-1779; 2214-0883; 2214-0883
• DOI: 10.1016/j.jpha.2022.04.001

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. [Display omitted] •Misfolded species of hIAPP form toxic oligomers in pancreatic β-cells.•hIAPP amyloids has been detected in the pancreas of about 90% subjects with T2DM.•Inhibitors of hIAPP aggregation can help manage T2DM.