Clark A, Chargé S B, Badman M K, de Koning E J
Diabetes Research Laboratories, Radcliffe Infirmary, Oxford, UK.
APMIS. 1996 Jan;104(1):12-8. doi: 10.1111/j.1699-0463.1996.tb00680.x.
Amyloid deposits are found in pancreatic islets of 90% of type 2 (non-insulin-dependent) diabetic subjects at postmortem. Islet amyloid is formed from islet amyloid polypeptide (IAPP). IAPP is a 37 amino acid peptide which is a normal constituent of beta cells and is co-secreted with insulin in animals and in man. The causative factors for fibrillogenesis of IAPP are unclear, but could be related to the sequence of IAPP and abnormal production of the peptide. The lack of islet amyloid in rodent models of diabetes is due to proline substitutions in the amyloidogenic region of IAPP. Amyloid fibrils are deposited between beta cells and islet capillaries: fibrils in invaginations of the plasma membrane may interfere with membrane signalling and insulin release. Amyloid fibrils are formed within 2 days in culture in islets isolated from transgenic mice expressing the gene for human IAPP, but not in vivo. Overexpression and decreased clearance of human IAPP from islet spaces may be important factors. Progressive deposition of IAPP fibrils combined with the associated reduction in the insulin-secreting beta cells is likely to contribute to deterioration of islet function in the course of type 2 diabetes.
在尸检时，90%的2型（非胰岛素依赖型）糖尿病患者的胰岛中发现有淀粉样沉积物。胰岛淀粉样物质由胰岛淀粉样多肽（IAPP）形成。IAPP是一种由37个氨基酸组成的肽，是β细胞的正常成分，在动物和人类中与胰岛素共同分泌。IAPP纤维形成的致病因素尚不清楚，但可能与IAPP的序列和该肽的异常产生有关。糖尿病啮齿动物模型中缺乏胰岛淀粉样物质是由于IAPP淀粉样生成区域中的脯氨酸替代。淀粉样纤维沉积在β细胞和胰岛毛细血管之间：质膜内陷中的纤维可能会干扰膜信号传导和胰岛素释放。从表达人IAPP基因的转基因小鼠分离的胰岛中，淀粉样纤维在培养2天内形成，但在体内不会形成。人IAPP从胰岛间隙中的过度表达和清除减少可能是重要因素。IAPP纤维的渐进性沉积与胰岛素分泌β细胞的相关减少相结合，可能会导致2型糖尿病病程中胰岛功能的恶化。
