Research progress on the correlation between islet amyloid peptides and type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and β-cell dysfunction. A hallmark of T2DM pathology is the accumulation of toxic amyloid polypeptides in and around pancreatic islet cells, leading to the progressive loss of β-cell populations. Human islet amyloid polypeptide (hIAPP), also known as amylin, is a 37-amino acid peptide hormone primarily produced by pancreatic β-cells. hIAPP aggregation and amyloid formation are strongly correlated with β-cell death and disease severity in T2DM patients. Objectives: This article aims to review the current research progress on the correlation between hIAPP and T2DM, focusing on the molecular mechanisms and potential therapeutic strategies. Methods: We conducted a comprehensive literature review covering recent studies on the molecular structure, physiological function, and pathological mechanisms of hIAPP. Key areas include biosynthesis, monomer structure, and the formation of hIAPP fiber structures. Additionally, we examined the mechanisms of hIAPP-induced β-cell death, including oxidative stress (OS), endoplasmic reticulum stress (ERS), impaired cell membrane and mitochondrial functions, and inflammatory factors. Results: Our review highlights the critical role of hIAPP in the pathogenesis of T2DM. Specifically, we found that hIAPP biosynthesis and monomer structure contribute to its physiological functions, while hIAPP aggregation forms toxic amyloid fibers, contributing to β-cell dysfunction. OS, ERS, impaired cell membrane and mitochondrial functions, and inflammatory factors play significant roles in hIAPP-induced β-cell death. There is a strong correlation between hIAPP aggregation and the severity of T2DM, and potential therapeutic approaches using small molecule inhibitors to prevent hIAPP aggregation and fibrosis are discussed. Conclusion: Understanding the molecular mechanisms of hIAPP in T2DM provides insights into potential therapeutic targets and preventive strategies. Future research should focus on developing more effective treatments targeting hIAPP aggregation and its downstream effects.