Balali-Mood Kia, Ashley Richard H, Hauss Thomas, Bradshaw Jeremy P
Veterinary Biomedical Sciences, R(D)SVS, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, UK.
FEBS Lett. 2005 Feb 14;579(5):1143-8. doi: 10.1016/j.febslet.2004.12.085.
Human islet amyloid polypeptide (hIAPP) forms amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM). Pre-fibrillar hIAPP oligomers (in contrast to monomeric IAPP or mature fibrils) increase membrane permeability, suggesting an important role in the disease. In the first structural study of membrane-associated hIAPP, lamellar neutron diffraction shows that oligomeric hIAPP inserts into phospholipid bilayers, and extends across the membrane. Rifampicin, which inhibits hIAPP-induced membrane permeabilisation in functional studies, prevents membrane insertion. In contrast, rat IAPP (84% identical to hIAPP, but non-amyloidogenic) does not insert into bilayers. Our findings are consistent with the hypothesis that membrane-active pre-fibrillar hIAPP oligomers insert into beta cell membranes in NIDDM.
人胰岛淀粉样多肽（hIAPP）在非胰岛素依赖型糖尿病（NIDDM）中形成淀粉样沉积物。与单体IAPP或成熟纤维不同，前纤维状hIAPP寡聚体增加膜通透性，提示其在该疾病中起重要作用。在首次对膜相关hIAPP的结构研究中，层状中子衍射显示寡聚体hIAPP插入磷脂双层，并穿过膜。在功能研究中抑制hIAPP诱导的膜通透性的利福平可阻止膜插入。相比之下，大鼠IAPP（与hIAPP有84%的同源性，但不形成淀粉样物质）不插入双层膜。我们的发现与以下假设一致：在NIDDM中，具有膜活性的前纤维状hIAPP寡聚体插入β细胞膜。
