Abstract：
BACKGROUND: Glucagon and insulin are the two most important hormones in glucose metabolism and have been incorporated in the dual-hormonal artificial pancreas, a device for automated glucose regulation for people with diabetes type 1. Currently the subcutis is the preferred site of hormone delivery for insulin-only as well as dual-hormonal artificial pancreas systems. The delay in glucose-lowering effect after subcutaneous injection of insulin is substantial, in contrast to the elevation of blood glucose values after subcutaneously injected glucagon which is occurs shortly after injection. We hypothesize that this is caused by properties of glucagon and have investigated the vasodilative effect of glucagon on subcutaneous blood flow in this proof-of-concept study.
METHODS: Twenty-two volunteers received subcutaneous injections of 0.1 mg and 0.01 mg glucagon, and saline on the abdomen. Blood flow was measured by a laser doppler blood flowmeter for 35 min after injections.
RESULTS: Injection of 0.1 mg glucagon resulted in a significant increase in blood flow compared with baseline blood flow for all time intervals. Significant increase was also observed after the 0.01 mg glucagon injection, except between two- and five-min post injection. The inter-individual variance was large and a third of the subjects did not show an apparent increase in local subcutaneous blood flow after the 0.1 mg glucagon injection.
CONCLUSIONS: This proof-of-concept study shows that micro-boluses of glucagon increases local subcutaneous blood flow on the abdomen of non-diabetic subjects. However, the vasodilative effect of glucagon is not observed in all subjects. The trial was not registered to protect intellectual property rights.
METHODS: Twenty-two volunteers received subcutaneous injections of 0.1 mg and 0.01 mg glucagon, and saline on the abdomen. Blood flow was measured by a laser doppler blood flowmeter for 35 min after injections.
RESULTS: Injection of 0.1 mg glucagon resulted in a significant increase in blood flow compared with baseline blood flow for all time intervals. Significant increase was also observed after the 0.01 mg glucagon injection, except between two- and five-min post injection. The inter-individual variance was large and a third of the subjects did not show an apparent increase in local subcutaneous blood flow after the 0.1 mg glucagon injection.
CONCLUSIONS: This proof-of-concept study shows that micro-boluses of glucagon increases local subcutaneous blood flow on the abdomen of non-diabetic subjects. However, the vasodilative effect of glucagon is not observed in all subjects. The trial was not registered to protect intellectual property rights.
摘要：
背景：胰高血糖素和胰岛素是葡萄糖代谢中两种最重要的激素，并且已被纳入双激素人工胰腺中，一种用于1型糖尿病患者的自动血糖调节装置。目前，对于仅胰岛素以及双激素人工胰腺系统，皮下组织是激素递送的首选部位。皮下注射胰岛素后的降糖效果延迟很大，与皮下注射胰高血糖素后血糖值升高相反，后者在注射后不久发生。我们假设这是由胰高血糖素的特性引起的，并在这项概念验证研究中研究了胰高血糖素对皮下血流的血管舒张作用。
方法：22名志愿者皮下注射0.1mg和0.01mg胰高血糖素，和盐水在腹部。注射后35分钟，通过激光多普勒血流计测量血流量。
结果：在所有时间间隔内，注射0.1mg胰高血糖素均导致血流量与基线血流量显着增加。注射0.01mg胰高血糖素后也观察到显着增加，除了注射后两分钟到五分钟。个体间的差异很大，三分之一的受试者在注射0.1mg胰高血糖素后没有显示出局部皮下血流量的明显增加。
结论：这项概念验证研究表明，胰高血糖素微丸可增加非糖尿病受试者腹部的局部皮下血流量。然而,并非在所有受试者中都观察到胰高血糖素的血管舒张作用。该审判没有注册以保护知识产权。
方法：22名志愿者皮下注射0.1mg和0.01mg胰高血糖素，和盐水在腹部。注射后35分钟，通过激光多普勒血流计测量血流量。
结果：在所有时间间隔内，注射0.1mg胰高血糖素均导致血流量与基线血流量显着增加。注射0.01mg胰高血糖素后也观察到显着增加，除了注射后两分钟到五分钟。个体间的差异很大，三分之一的受试者在注射0.1mg胰高血糖素后没有显示出局部皮下血流量的明显增加。
结论：这项概念验证研究表明，胰高血糖素微丸可增加非糖尿病受试者腹部的局部皮下血流量。然而,并非在所有受试者中都观察到胰高血糖素的血管舒张作用。该审判没有注册以保护知识产权。
