Department Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
Department Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
BMJ Open Diabetes Res Care. 2021 Jan;9(1). doi: 10.1136/bmjdrc-2020-001929.
The effect of intraperitoneal insulin infusion has limited evidence in the literature. Therefore, the aim of the study was to investigate the pharmacokinetics and pharmacodynamics of different intraperitoneal insulin boluses. There is a lack of studies comparing the insulin appearance in the systemic circulation after intraperitoneal compared with subcutaneous insulin delivery. Thus, we also aimed for a comparison with the subcutaneous route.
Eight anesthetized, non-diabetic pigs were given three different intraperitoneal insulin boluses (2, 5 and 10 U). The order of boluses for the last six pigs was randomized. Endogenous insulin and glucagon release were suppressed by repeated somatostatin analog injections. The first pig was used to identify the infusion rate of glucose to maintain stable glucose values throughout the experiment. The estimated difference between insulin boluses was compared using two-way analysis of variance (GraphPad Prism V.8).In addition, a trial of three pigs which received subcutaneous insulin boluses was included for comparison with intraperitoneal insulin boluses.
Decreased mean blood glucose levels were observed after 5 and 10 U intraperitoneal insulin boluses compared with the 2 U boluses. No changes in circulating insulin levels were observed after the 2 and 5 U intraperitoneal boluses, while increased circulating insulin levels were observed after the 10 U intraperitoneal boluses. Subcutaneously injected insulin resulted in higher values of circulating insulin compared with the corresponding intraperitoneal boluses.
Smaller intraperitoneal boluses of insulin have an effect on circulating glucose levels without increasing insulin levels in the systemic circulation. By increasing the insulin bolus, a major increase in circulating insulin was observed, with a minor additive effect on circulating glucose levels. This is compatible with a close to 100% first-pass effect in the liver after smaller intraperitoneal boluses. Subcutaneous insulin boluses markedly increased circulating insulin levels.
腹腔内胰岛素输注的效果在文献中证据有限。因此，本研究旨在探讨不同腹腔内胰岛素推注的药代动力学和药效学。目前缺乏比较腹腔内与皮下胰岛素给药后胰岛素在体循环中出现情况的研究。因此，我们也旨在与皮下途径进行比较。
8 头麻醉、非糖尿病猪分别接受 3 种不同剂量的腹腔内胰岛素推注（2、5 和 10 U）。最后 6 头猪的推注顺序随机化。重复给予生长抑素类似物以抑制内源性胰岛素和胰高血糖素释放。第一头猪用于确定葡萄糖输注率，以维持整个实验过程中的血糖稳定。使用双向方差分析（GraphPad Prism V.8）比较胰岛素推注之间的差异。此外，还包括 3 头接受皮下胰岛素推注的猪的试验，以与腹腔内胰岛素推注进行比较。
与 2 U 推注相比，5 U 和 10 U 腹腔内胰岛素推注后平均血糖水平降低。2 U 和 5 U 腹腔内推注后循环胰岛素水平无变化，而 10 U 腹腔内推注后循环胰岛素水平升高。与相应的腹腔内推注相比，皮下注射胰岛素导致循环胰岛素水平更高。
较小剂量的腹腔内胰岛素推注可降低循环血糖水平，而不会增加系统循环中的胰岛素水平。增加胰岛素推注量会导致循环胰岛素水平显著增加，而对循环血糖水平的附加作用较小。这与较小剂量腹腔内推注后肝脏几乎 100%的首过效应相符。皮下胰岛素推注可显著增加循环胰岛素水平。
