2 型糖尿病患者胰岛中的胰岛淀粉样多肽。
Islet amyloid polypeptide in pancreatic islets from type 2 diabetic subjects.
机构信息
Department of Integrative Bioscience, Oregon National Primate Center, Oregon Health and Science University, Portland, OR, USA.
出版信息
Islets. 2012 May-Jun;4(3):223-32. doi: 10.4161/isl.20477.
AIMS/HYPOTHESIS: Islet amyloid polypeptide (IAPP) is a chief constituent of amyloid deposits in pancreatic islets, characteristic histopathology for type 2 diabetes. The goal of this study was to analyze islet cell composition in diabetic islets for the process of transforming water-soluble IAPP in β-cells to water-insoluble amyloid deposits by Immunocytochemical staining using different dilutions of anti-IAPP antibody. IAPP in β-cell granules may initiate β-cell necrosis through apoptosis to form interstitial amyloid deposits in type 2 diabetic islets.
RESULTS
Control islets revealed twice as much β-cells as α-cells whereas 15 of 18 type 2 diabetic cases (83%) revealed α- cells as major cells in larger islets. Diabetic islets consisted of more larger islets with more σ-cells than β-cells, which contribute to hyperglucagonemia. In control islets, percentage of IAPP-positive cells against β-cells was 40-50% whereas percentage for type 2 diabetic islets was about 25%. Amyloid deposits in diabetic islets were not readily immunostained for IAPP using 1: 800 diluted antibody, however, 1: 400 and 1: 200 diluted solutions provided stronger immunostaining in early stages of islet amyloidogenesis after treating the deparaffinized sections with formic acid.
METHODS
Using commercially available rabbit antihuman IAPP antibody, immunocytochemical staining was performed on 18 cases of pancreatic tissues from type 2 diabetic subjects by systematically immunostaining for insulin, glucagon, somatostatin (SRIF) and IAPP compared with controls. Sizes of islets were measured by 1 cm scale, mounted in 10X eye piece.
CONCLUSIONS/INTERPRETATION: α cells were major islet cells in majority of diabetic pancreas (83%) and all diabetic islets contained less IAPP-positive cells than controls, indicating that IAPP deficiency in pancreatic islets is responsible for decreased IAPP in blood. In diabetic islets, water-soluble IAPP disappeared in β-cell granules, which transformed to water-insoluble amyloid deposits. Amyloid deposits were not readily immunostained using IAPP 1: 800 diluted antibody but were stronger immunostained for IAPP in early stages of amyloid deposited islets using less diluted solutions after formic acid treatment. In early islet amyloidogenesis, dying β-cell cytoplasm was adjacently located to fine amyloid fibrils, supporting that IAPP in secretary granules from dying β cells served as nidus for islet β-sheet formation.
目的/假设：胰岛淀粉样多肽（IAPP）是胰岛中淀粉样沉积的主要成分，也是 2 型糖尿病的特征性组织病理学表现。本研究的目的是通过使用不同稀释度的抗 IAPP 抗体进行免疫细胞化学染色，分析糖尿病胰岛中胰岛细胞的组成，以了解将β细胞中可溶性的 IAPP 转化为不溶性淀粉样沉积物的过程。β细胞颗粒中的 IAPP 可能通过细胞凋亡引发β细胞坏死，从而在 2 型糖尿病胰岛中形成间质淀粉样沉积物。
结果
对照胰岛中β细胞的数量是α细胞的两倍，而 18 例 2 型糖尿病病例中有 15 例（83%）的胰岛中α细胞是主要细胞，且这些胰岛较大。糖尿病胰岛包含更多的大胰岛，其中β细胞比 σ细胞多，这导致高胰高血糖素血症。在对照胰岛中，IAPP 阳性细胞对β细胞的百分比为 40-50%，而 2 型糖尿病胰岛的百分比约为 25%。使用 1:800 稀释的抗体对糖尿病胰岛中的淀粉样沉积物进行免疫染色时，淀粉样沉积物不易被染色，但在用甲酸处理脱蜡切片后，使用 1:400 和 1:200 稀释的溶液进行早期胰岛淀粉样生成免疫染色时，染色强度更强。
方法
使用商业上可获得的兔抗人 IAPP 抗体，通过系统地对胰岛素、胰高血糖素、生长抑素（SRIF）和 IAPP 进行免疫染色，对 18 例 2 型糖尿病患者的胰腺组织进行免疫细胞化学染色，并与对照组进行比较。通过 1cm 标尺测量胰岛的大小，并安装在 10X 目镜中。
结论/解释：在大多数糖尿病胰腺中（83%），α细胞是主要的胰岛细胞，并且所有糖尿病胰岛中的 IAPP 阳性细胞都少于对照组，这表明胰岛中 IAPP 的缺乏导致血液中 IAPP 的减少。在糖尿病胰岛中，β细胞颗粒中的水溶性 IAPP 消失，转化为不溶性淀粉样沉积物。使用 1:800 稀释的抗体对淀粉样沉积物进行免疫染色时，淀粉样沉积物不易被染色，但在用甲酸处理后，使用较低稀释度的溶液进行早期淀粉样沉积胰岛的免疫染色时，IAPP 的染色强度更强。在早期胰岛淀粉样生成中，垂死的β 细胞质与细小的淀粉样纤维相邻，这支持了来自垂死β 细胞的分泌颗粒中的 IAPP 作为胰岛β 片层形成的核心。
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