Watanabe R M, Vølund A, Bergman R N
University of Southern California School of Medicine, Department of Physiology and Biophysics, Los Angeles 90033.
Diabetes Care. 1991 Nov;14(11):1021-30. doi: 10.2337/diacare.14.11.1021.
To determine the bioavailability and bioactivity of subcutaneously injected insulin.
A randomized block design with six male mongrel dogs as subjects. In protocol 1, purified pork insulin was infused intravenously to simulate the pattern of appearance in the blood that would have been expected from subcutaneous injection. Three intravenous doses (0.05, 0.10, and 0.15 U/kg) were infused on separate days in a pattern (0-300 min) designed to approximately simulate the absorption rate of subcutaneously injected insulin. In protocol 2, interscapular subcutaneous injections of pork insulin at 0.10 U/kg were made.
Integrated insulin, decrement in plasma glucose, and maximal glucose clearance for subcutaneous injection experiments were similar to intravenous infusion of equal dose (P greater than 0.10) but significantly different from low-dose infusions (P less than 0.025). Similar results were observed for hepatic glucose output and glucose uptake. Hypoglycemia elicited counterregulatory responses that appeared to be under a threshold differentiated at a plasma glucose of approximately 3 mM. Integrated insulin was plotted against insulin dose to create dose-response curves for intravenous data. The curve was then used to predict the actual appearance rate of insulin in plasma for subcutaneous injection. The estimated bioavailability of subcutaneous insulin was 103.0 +/- 10.5% of the injected dose.
We concluded that, in dogs, insulin delivered subcutaneously in the interscapular area is not significantly degraded before absorption, resulting in metabolic effects equal to intravenous insulin infusion of equivalent dose.
测定皮下注射胰岛素的生物利用度和生物活性。
采用随机区组设计，以6只雄性杂种犬为研究对象。在方案1中，静脉输注纯化的猪胰岛素，以模拟皮下注射后预期的血药浓度变化模式。在不同日期分别静脉输注3种剂量（0.05、0.10和0.15 U/kg），输注模式（0 - 300分钟）旨在大致模拟皮下注射胰岛素的吸收速率。在方案2中，于肩胛间皮下注射0.10 U/kg的猪胰岛素。
皮下注射实验的整合胰岛素、血糖降低幅度和最大葡萄糖清除率与等剂量静脉输注相似（P大于0.10），但与低剂量输注显著不同（P小于0.025）。肝葡萄糖输出和葡萄糖摄取也观察到类似结果。低血糖引发的反调节反应似乎在血浆葡萄糖约为3 mM时的一个阈值以下出现。将整合胰岛素与胰岛素剂量作图，以生成静脉注射数据的剂量反应曲线。然后用该曲线预测皮下注射时胰岛素在血浆中的实际出现速率。皮下胰岛素的估计生物利用度为注射剂量的103.0 +/- 10.5%。
我们得出结论，在犬中，肩胛间区域皮下注射的胰岛素在吸收前未显著降解，产生的代谢效应与等剂量静脉输注胰岛素相当。
