Abstract: Zebrafish (Danio rerio) shows persistent hyperglycemia under glucose loading status. Compared with control group which was only injected intraperitoneally with sterilized deionized water, the expression of insulin gene was significantly up-regulated in glucose group which was only injected intraperitoneally with glucose, while there were no significant differences in plasma insulin level and the expression of hepato-pancreas glucose transporters genes. The result indicated that insufficient insulin secretion and delayed glucose transport of zebrafish would result in persistent hyperglycemia. In order to observe the effect of exogenous insulin on blood glucose and its transport in vivo, we designed low (1.25 IU/kg), medium (12.5 IU/kg) and high (125 IU/kg) concentrations of insulin, and co-injected zebrafish with glucose (0.1 g/mL), and then observed the changes of blood glucose. The low dose of exogenous insulin was found to be the optimal injection concentration, which could effectively promote the reduction of blood glucose in zebrafish, and could directly reflect the change of blood glucose after glucose loading. Also, the research showed that the changes of blood glucose were not affected by gender. At the optimal injection concentration of insulin, insulin group (co-injection of glucose with insulin) could significantly reduce the time of blood glucose recovering to normal level when compared with glucose group. And further analysis showed that plasma insulin level increased and the expression of glucose transporters genes were significantly up-regulated, however, the expression of insulin gene was significantly inhibited. Taken together, the above results indicated that insufficient insulin secretion and delayed glucose transport were the causes of persistent hyperglycemia in zebrafish, and exogenous insulin could promote the decrease of blood glucose, whereas it could feedback suppress the expression of insulin gene in hepatopancreas.

Key words: zebrafish (Danio rerio), insulin, blood glucose, GLUTs

摘要： 斑马鱼（Danio rerio）在糖负荷状态下表现出持续高血糖现象。与对照组（仅腹腔注射灭菌去离子水）相比，葡萄糖组（仅腹腔注射葡萄糖）血浆胰岛素水平无显著差异，胰岛素基因表达显著上调，肝胰脏葡萄糖转运蛋白（glucose transporters，GLUTs）基因表达无显著差异，说明斑马鱼自身胰岛素分泌不足和葡萄糖转运迟缓是导致其在糖负荷状态下持续高血糖的原因。为了观察外源性胰岛素对斑马鱼血糖及其在体内转运的影响，设计低（1.25 IU/kg）、中（12.5 IU/kg）、高（125 IU/kg）3个浓度的胰岛素，分别与葡萄糖溶液（0.1 g/mL）共注射斑马鱼并观察其血糖变化。结果表明，低剂量胰岛素能有效促进斑马鱼血糖的降低，且能直观反映糖负荷后血糖的变化情况，为最适注射浓度。此外，研究显示斑马鱼血糖变化不受性别影响。在胰岛素最适注射浓度下，与葡萄糖组相比，胰岛素组（葡萄糖与胰岛素共注射）可以显著减少斑马鱼血糖恢复到正常水平的时间，进一步分析发现，斑马鱼血浆胰岛素水平增加，肝胰脏葡萄糖转运蛋白基因表达显著上调，但胰岛素基因表达却被显著抑制。综上所述，胰岛素分泌不足和葡萄糖转运迟缓是造成斑马鱼持续高血糖的原因；外源性胰岛素能够促进糖负荷状态下斑马鱼血糖的降低，但是具有反馈抑制斑马鱼肝胰脏胰岛素基因表达的作用。

关键词: 斑马鱼, 胰岛素, 血糖, 葡萄糖转运蛋白