Agren U M, Launiala K, Knip M, Simell O
Department of Anatomy, University of Kuopio, Finland.
Pancreas. 1995 Mar;10(2):131-6. doi: 10.1097/00006676-199503000-00004.
We studied the effects of alloxan on insulin and glucagon secretion, islet insulin content, and morphology of human fetal islet-like cell clusters (ICCs). ICCs were derived after collagenase digestion and culture of pancreata from two fetuses. Culture medium (RPMI 1640) containing either 2.0 (low) or 11.1 (high) mM glucose was used during the alloxan exposure. Alloxan exposure lasted for 5 min at room temperature, with final concentrations of 0.3, 1, 3, 10, 30 and 100 mM. Medium samples were collected for hormone assays on days 0, 1, 2, 3, 6, and 10 and islet insulin contents were measured on day 10 after alloxan treatment. Electron microscopy of ICCs was done 24 h after the drug exposure. Control ICCs steadily increased their insulin secretion during the whole study period. Alloxan concentrations above 0.3 mM significantly (p < 0.01) decreased insulin secretion at the low glucose concentration. High glucose protected beta cells from alloxan toxicity. There was no difference in islet insulin contents between alloxan-treated and control cultures. Glucagon secretion by glucose media was not affected by alloxan exposure. All islet cells including beta cells remained intact in electron microscopy. The results suggest a block in insulin secretion by alloxan, but beta cells appear to recover at least partly in their insulin-secreting capacity.
我们研究了四氧嘧啶对人胎儿胰岛样细胞簇（ICC）胰岛素和胰高血糖素分泌、胰岛胰岛素含量及形态的影响。ICC是通过对两个胎儿的胰腺进行胶原酶消化和培养后获得的。在四氧嘧啶暴露期间，使用含有2.0（低）或11.1（高）mM葡萄糖的培养基（RPMI 1640）。四氧嘧啶在室温下暴露5分钟，最终浓度为0.3、1、3、10、30和100 mM。在第0、1、2、3、6和10天收集培养基样本进行激素测定，并在四氧嘧啶处理后第10天测量胰岛胰岛素含量。药物暴露24小时后对ICC进行电子显微镜检查。在整个研究期间，对照ICC的胰岛素分泌持续增加。在低葡萄糖浓度下，高于0.3 mM的四氧嘧啶浓度显著（p<0.01）降低胰岛素分泌。高葡萄糖可保护β细胞免受四氧嘧啶毒性。四氧嘧啶处理组和对照组培养物之间的胰岛胰岛素含量没有差异。葡萄糖培养基中的胰高血糖素分泌不受四氧嘧啶暴露的影响。在电子显微镜下，包括β细胞在内的所有胰岛细胞均保持完整。结果表明四氧嘧啶可阻断胰岛素分泌，但β细胞的胰岛素分泌能力似乎至少部分得以恢复。
