Re C A, Veroni M C, Larkins R G
Diabetologia. 1984 Apr;26(4):304-9. doi: 10.1007/BF00283655.
The effect of islet activating protein on glucose tolerance, insulin secretion and insulin responsiveness was studied in the NZO mouse, a model of non-insulin dependent diabetes and obesity. A single IV injection of 5 ng/g body weight islet activating protein markedly lowered plasma glucose and the glucose response to IP glucose administration, measured 5 days later (mean +/- SEM, plasma glucose levels 0, 10, 30 and 60 min after glucose 6.0 +/- 0.9, 14.6 +/- 1.3, 14.1 +/- 1.3 and 13.2 +/- 1.7 mmol/l in islet activating protein-treated NZO mice versus 12.8 +/- 1.6, 27.8 +/- 3.4, 34.7 +/- 4.1, 39.1 +/- 3.8 mmol/l in carrier-treated NZO mice). There was no difference in fasting plasma insulin levels between islet activating protein and carrier-treated mice. No response of plasma insulin to glucose occurred in the carrier-treated mice, but a highly significant insulin response to glucose was seen in the islet activating protein-treated mice. The in vitro responsiveness of pancreatic islets of islet activating protein-treated NZO mice to glucose was improved, and the inhibitory effect of adrenaline on insulin secretion was reduced. The in vivo hypoglycaemic response to exogenous insulin was not improved by islet activating protein and a demonstrated defect in the insulin sensitivity and responsiveness of glucose utilization by isolated soleus muscle was not reversed by islet activating protein treatment. It is concluded that islet activating protein is highly effective in improving glucose tolerance and insulin secretion in NZO mice, and that the improvement in glucose tolerance occurs without demonstrable improvement in the responsiveness to exogenous insulin or sensitivity of soleus muscle to insulin.
在非胰岛素依赖型糖尿病和肥胖模型NZO小鼠中，研究了胰岛激活蛋白对葡萄糖耐量、胰岛素分泌及胰岛素反应性的影响。单次静脉注射5 ng/g体重的胰岛激活蛋白可显著降低血浆葡萄糖水平以及对腹腔注射葡萄糖的葡萄糖反应，于5天后测量（平均值±标准误，胰岛激活蛋白处理的NZO小鼠在葡萄糖注射后0、10、30和60分钟时的血浆葡萄糖水平分别为6.0±0.9、14.6±1.3、14.1±1.3和13.2±1.7 mmol/L，而载体处理的NZO小鼠分别为12.8±1.6、27.8±3.4、34.7±4.1和39.1±3.8 mmol/L）。胰岛激活蛋白处理组和载体处理组小鼠的空腹血浆胰岛素水平无差异。载体处理组小鼠的血浆胰岛素对葡萄糖无反应，但胰岛激活蛋白处理组小鼠对葡萄糖有高度显著的胰岛素反应。胰岛激活蛋白处理的NZO小鼠的胰岛对葡萄糖的体外反应性得到改善，肾上腺素对胰岛素分泌的抑制作用降低。胰岛激活蛋白未改善对外源性胰岛素的体内降血糖反应，且未逆转离体比目鱼肌对葡萄糖利用的胰岛素敏感性和反应性所显示的缺陷。结论是，胰岛激活蛋白在改善NZO小鼠的葡萄糖耐量和胰岛素分泌方面非常有效，且葡萄糖耐量的改善并未伴随着对外源性胰岛素反应性或比目鱼肌对胰岛素敏感性的明显改善。
