Glucagon is a pancreatic hormone and increases the blood glucose levels. it may be incorporated in a dual hormone artificial pancreas, a device to automatically and continuously control blood glucose levels of individuals with diabetes. Artificial pancreas systems have been developed for use in the subcutaneous tissue; however, the systems are not fully automated due to slow dynamics. The intraperitoneal space is therefore investigated as an alternative location for an artificial pancreas. Glucose dynamics after subcutaneous and intraperitoneal glucagon delivery in ten anaesthetized pigs were investigated. The pigs received intraperitoneal boluses of 0.3 µg/kg and 0.6 µg/kg and a subcutaneous bolus of 0.6 µg/kg in randomized order. They also received an intraperitoneal bolus of 1 mg given at the end of the experiments to test the remaining capacity of rapid glucose release. Six pigs were included in the statistical analysis. The intraperitoneal glucagon bolus of 0.6 µg/kg gave a significantly higher glucose response from 14 to 30 min compared with the subcutaneous bolus. the results indicate that glucagon induces a larger glucose response after intraperitoneal delivery compared with subcutaneous delivery and is encouraging for the incorporation of glucagon in an intraperitoneal artificial pancreas.

ObjectiveHypoglycemia is a frequent and potentially dangerous event among patients with diabetes mellitus type 1. Subcutaneous glucagon is an emergency treatment to counteract severe hypoglycemia. The effect of intraperitoneal glucagon delivery is sparsely studied. We performed a direct comparison of the blood glucose response following intraperitoneally, subcutaneously and intravenously administered glucagon.Research design and methodsThis is a prospective, randomized, controlled, open-label, crossover trial in 20 octreotide-treated rats. Three interventions, 1  week apart, in a randomized order, were done in each rat. All 20 rats were given intraperitoneal and subcutaneous glucagon injections, from which 5 rats were given intravenous glucagon injections and 15 rats received placebo (intraperitoneal isotonic saline) injection. The dose of glucagon was 5 µg/kg body weight for all routes of administration. Blood glucose levels were measured before and until 60 min after the glucagon/placebo injections.ResultsCompared with placebo-treated rats, a significant increase in blood glucose was observed 4 min after intraperitoneal glucagon administration (p=0.009), whereas after subcutaneous and intravenous glucagon administration significant increases were seen after 8 min (p=0.002  and p<0.001, respectively). In intraperitoneally treated compared with subcutaneously treated rats, the increase in blood glucose was higher after 4 min (p=0.019) and lower after 40 min (p=0.005) and 50 min (p=0.011). The maximum glucose response occurred earlier after intraperitoneal compared with subcutaneous glucagon injection (25 min vs 35 min; p=0.003).ConclusionsGlucagon administered intraperitoneally gives a faster glucose response compared with subcutaneously administered glucagon in rats. If repeatable in humans, the more rapid glucose response may be of importance in a dual-hormone artificial pancreas using the intraperitoneal route for administration of insulin and glucagon.

BackgroundIn diabetes research, the development of the artificial pancreas has been a major topic since continuous glucose monitoring became available in the early 2000’s. A prerequisite for an artificial pancreas is fast and reliable glucose sensing. However, subcutaneous continuous glucose monitoring carries the disadvantage of slow dynamics. As an alternative, we explored continuous glucose sensing in the peritoneal space, and investigated potential spatial differences in glucose dynamics within the peritoneal cavity. As a secondary outcome, we compared the glucose dynamics in the peritoneal space to the subcutaneous tissue.Material and methodsEight-hour experiments were conducted on 12 anesthetised non-diabetic pigs. Four commercially available amperometric glucose sensors (FreeStyle Libre, Abbott Diabetes Care Ltd., Witney, UK) were inserted in four different locations of the peritoneal cavity and two sensors were inserted in the subcutaneous tissue. Meals were simulated by intravenous infusions of glucose, and frequent arterial blood and intraperitoneal fluid samples were collected for glucose reference.ResultsNo significant differences were discovered in glucose dynamics between the four quadrants of the peritoneal cavity. The intraperitoneal sensors responded faster to the glucose excursions than the subcutaneous sensors, and the time delay was significantly smaller for the intraperitoneal sensors, but we did not find significant results when comparing the other dynamic parameters.

IntroductionThe 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.Research design and methodsEight 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.ResultsDecreased 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.ConclusionsSmaller 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.