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| Title | Structure of pancreatic hIAPP fibrils derived from patients with type 2 diabetes. |
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| Journal, issue, pages | Cell, Year 2026 |
| Publish date | Jan 2, 2026 |
 Authors | Wenjing Liu / Jianting Han / Wei Gong / Fei Zhang / Qin Cao /  |
| PubMed Abstract | Type 2 diabetes (T2D) impacts the quality of life and lifespan of nearly 10% of the global population. Human islet amyloid polypeptide (hIAPP) constitutes a major component of islet amyloid ...Type 2 diabetes (T2D) impacts the quality of life and lifespan of nearly 10% of the global population. Human islet amyloid polypeptide (hIAPP) constitutes a major component of islet amyloid deposition in patients with T2D, with hIAPP fibrils believed to play a key role in the pathogenesis of T2D. In this study, we determined the cryo-electron microscopy (cryo-EM) structure of hIAPP fibrils extracted from surgically resected pancreases of three donors with T2D. These fibrils exhibit a uniform morphology, comprising two symmetrical protofilaments encompassing residues 2-37 of hIAPP and adopting an Ω-shaped fold. The structure of pancreatic hIAPP fibrils differs from that of fibrils formed in vitro. Additional densities were observed in the pancreatic hIAPP fibrils, suggesting ligand binding that may play significant roles in the pathogenesis of T2D. Collectively, our study presents the atomic structure of pathological hIAPP fibrils, contributing to the therapeutic and mechanistic exploration of T2D. |
 External links | Cell / PubMed:41483806 |
| Methods | EM (helical sym.) |
| Resolution | 2.9 - 3.42 Å |
| Structure data | EMDB-64268, PDB-9ulz:  EMDB-65046: Cryo-EM map of hIAPP fibrils extracted from a donor with T2D and pancreatic cancer  EMDB-65957: Cryo-EM map of hIAPP fibrils extracted from a donor with T2D and Intraductal Papillary Mucinous Neoplasm |
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 Keywords | PROTEIN FIBRIL / Amyloid fibrils / type II diabetes / hIAPP |
homo sapiens (human)