College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041, China.
Biochem Biophys Res Commun. 2012 Oct 26;427(3):513-7. doi: 10.1016/j.bbrc.2012.09.087. Epub 2012 Sep 26.
A large body of experimental evidence suggests that cytokines trigger pancreatic β-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.
大量实验证据表明细胞因子在 1 型糖尿病中引发胰岛β细胞死亡。Daintain/AIF-1（同种异体炎症因子-1）是活化巨噬细胞的特异性标志物，在糖尿病前期 BB 大鼠的胰岛中积累。在本研究中，我们证明了 Daintain/AIF-1 被释放到血液中，1 型糖尿病易感非肥胖型糖尿病（NOD）小鼠发生胰岛炎时血液中的 Daintain/AIF-1 水平明显高于健康 NOD 小鼠。当静脉注射到 NOD 小鼠中时，Daintain/AIF-1 刺激白细胞增殖，增加血糖浓度，损害胰岛素表达，上调胰腺中一氧化氮（NO）的产生，并加速 NOD 小鼠的糖尿病，而针对 Daintain/AIF-1 的抗体可延迟或预防 NOD 小鼠的胰岛炎。这些结果表明 Daintain/AIF-1 通过激活免疫细胞并诱导 NOD 小鼠胰腺中 NO 的产生而引发 1 型糖尿病。
