Cell重磅！糖尿病发病的“终极密码”被中国团队破译

Core Insights - The research published in Cell journal reveals the atomic structure of human islet amyloid polypeptide (hIAPP) fibrils extracted from type 2 diabetes patients, marking a significant advancement in understanding the disease mechanism and potential therapeutic targets [1][2][14]. Group 1: Research Findings - The study identifies a unique "Ω-shaped folding" of hIAPP, which is crucial in the pathology of type 2 diabetes, as it leads to the formation of amyloid fibrils that damage insulin-secreting β-cells [3][6]. - The research team utilized cryo-electron microscopy to directly observe the hIAPP fibrils from patient samples, confirming a highly uniform structure compared to the polymorphic forms seen in vitro [4][6]. - The study highlights the presence of six additional electron density regions in the structure, suggesting the involvement of other molecules (ligands) that stabilize the hIAPP fibrils [7][9]. Group 2: Implications for Diagnosis and Treatment - The findings provide a new understanding of the disease mechanism, proposing that unknown ligands, possibly lipids, play a critical role in driving the pathological folding of hIAPP [9][10]. - The research indicates a structural similarity between hIAPP fibrils and amyloid-beta (Aβ) fibrils found in Alzheimer's disease, suggesting a potential link between the two diseases and the possibility of developing treatments targeting both conditions [10][13]. - The study opens avenues for early diagnosis through the development of molecular imaging probes that can detect hIAPP deposits before clinical symptoms appear, as well as targeted therapies that could disrupt hIAPP fibril formation [13][14].