El-Khatib Firas H, Jiang John, Gerrity Ross G, Damiano Edward R
Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, USA.
Diabetes Technol Ther. 2007 Apr;9(2):135-44. doi: 10.1089/dia.2006.0006.
The objective of this study was to determine the in vivo pharmacodynamics of glucagon and to test its glycemic effect over days by assessing its time course of activity and potency in a type 1 diabetic swine model.
Individual experiments were conducted in different pigs using glucagon preparations that were reconstituted on different days and stored at room temperature or near body temperature before usage. All experiments involved a subcutaneous bolus of glucagon to counter impending hypoglycemia induced by an earlier bolus of fast-acting insulin. Frequent blood-glucose measurements, using a standard in vitro hand-held meter, were taken during each experiment to track variations in blood-glucose concentration.
Significant glucagon action was observed as early as 5 min after administration, as evidenced by an effective halt to declining blood glucose and a subsequent twofold rise in blood glucose after approximately 20 min. Results also indicate that the consumption of glucagon from the subcutaneous depot is substantially faster than that of fast-acting insulin. Furthermore, no significant depreciation was observed in glucagon efficacy across aging preparations as old as 7 days.
These results suggest profound utility of subcutaneous glucagon in a closed-loop glucose control system, especially since glucagon would provide an effective safeguarding measure to stave off impending hypoglycemia, an application where the rapid effect of subcutaneous glucagon is both serendipitous and essential. Despite the notion that the stability of glucagon in solution at room temperature is inferior to that of fast-acting insulin, its subcutaneous administration has promising prospects for long-term closed-loop ambulatory care.
本研究的目的是确定胰高血糖素的体内药效学，并通过评估其在1型糖尿病猪模型中的活性和效力的时间进程，来测试其数天内的血糖效应。
在不同的猪身上进行个体实验，使用在不同日期复溶并在使用前储存在室温或接近体温的胰高血糖素制剂。所有实验均涉及皮下注射一次胰高血糖素，以对抗早期快速起效胰岛素推注引起的即将发生的低血糖。在每个实验过程中，使用标准体外手持式血糖仪频繁测量血糖，以跟踪血糖浓度的变化。
给药后5分钟就观察到了显著的胰高血糖素作用，表现为血糖下降有效停止，约20分钟后血糖随后升高两倍。结果还表明，皮下储库中胰高血糖素的消耗速度明显快于快速起效胰岛素。此外，在长达7天的老化制剂中，未观察到胰高血糖素疗效有显著下降。
这些结果表明皮下注射胰高血糖素在闭环血糖控制系统中具有深远的应用价值，特别是因为胰高血糖素将提供一种有效的保护措施来避免即将发生的低血糖，在这种应用中，皮下注射胰高血糖素的快速作用既意外又至关重要。尽管有人认为胰高血糖素在室温溶液中的稳定性不如快速起效胰岛素，但其皮下给药在长期闭环门诊护理方面具有广阔前景。
