METHODS: We have investigated changes in α-cell lineage in response to 10-days treatment with artemether (100 mg/kg oral, once daily) on a background of β-cell stress induced by multiple low-dose streptozotocin (STZ) injection in GluCreERT2; ROSA26-eYFP transgenic mice.
RESULTS: Artemether intervention did not affect the actions of STZ on body weight, food and fluid intake or blood glucose. Circulating insulin and glucagon were reduced by STZ treatment, with a corresponding decline in pancreatic insulin content, which were not altered by artemether. The detrimental changes to pancreatic islet morphology induced by STZ were also evident in artemether-treated mice. Tracing of α-cell lineage, through co-staining for glucagon and yellow fluorescent protein (YFP), revealed a significant decrease of the proportion of glucagon+YFP- cells in STZ-diabetic mice, which was reversed by artemether. However, artemether had no effect on transdifferentiation of α-cells into β-cells and failed to augment the number of bi-hormonal, insulin+glucagon+, islet cells.
CONCLUSIONS: Our observations confirm that artemisinin derivatives do not impart meaningful benefits on islet cell lineage transition events or pancreatic islet morphology.
方法:我们研究了α细胞系对蒿甲醚(100mg/kg口服,每天一次)在GluCreERT2中多次低剂量链脲佐菌素(STZ)注射诱导的β细胞应激的背景下;ROSA26-eYFP转基因小鼠。
结果:Artemether干预没有影响STZ对体重的作用,食物和液体摄入量或血糖。STZ治疗降低循环胰岛素和胰高血糖素,随着胰腺胰岛素含量的相应下降,没有被蒿甲醚改变。STZ诱导的胰岛形态的有害变化在蒿甲醚处理的小鼠中也很明显。追踪α细胞谱系,通过胰高血糖素和黄色荧光蛋白(YFP)的共染色,显示STZ糖尿病小鼠中胰高血糖素+YFP-细胞的比例显着降低,被蒿甲醚逆转了。然而,蒿甲醚对α细胞转分化为β细胞没有影响,并且未能增加双激素的数量,胰岛素+胰高血糖素+,胰岛细胞。
结论:我们的观察结果证实,青蒿素衍生物对胰岛细胞谱系转变事件或胰岛形态没有赋予有意义的益处。