Intraperitoneal and subcutaneous glucagon delivery in anaesthetized pigs: effects on circulating glucagon and glucose levels

Abstract

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.

Pharmacokinetics of Intraperitoneally Delivered Glucagon in Pigs: A Hypothesis of First Pass Metabolism

“…Data for this study were retrieved from four series of experiments conducted by our research group (Artificial Pancreas Trondheim, APT) between 12 April 2018 and 16 January 2020 [21]. In some experiments, the doses were fixed at 12, 50, 75 or 150 µg rather than based on weight.…”

“…The effectiveness of somatostatin analogue treatment (SAT) has been evaluated in a previously published study by our research group [21]. The pigs were given SAT through either an IV infusion of 0.4 mg octreotide (Sandostatin ® ; Novartis Europharm, UK) every hour or a continuous IV infusion of 150 µg octreotide per hour to suppress their endogenous glucagon secretion.…”

“…In a previous study on rats, our research group observed accelerated onset of action of glucagon after IP compared to subcutaneous (SC) administration [22]. In another study on pigs, we demonstrated superior glucose response after IP delivery compared to SC administration [21]. However, both of these studies focussed on the pharmacodynamics of IP glucagon.…”

“…Insulin pumps with IP delivery have been tested on humans with some success [19,20]. In contrast, the effects of IP-administered glucagon have only been studied in a few animal trials [21][22][23][24]. In a previous study on rats, our research group observed accelerated onset of action of glucagon after IP compared to subcutaneous (SC) administration [22].…”

Investigation of the effect of clinically relevant interferents on glucose monitoring using near‐infrared spectroscopy

“…Porcine samples of intraperitoneal fluid was collected from two pigs during unpublished pilot experiments (date: 6 June 2019 and 11 June 2019, kept frozen) performed similarly to other work from our group [36,37]. The intraperitoneal fluid samples were spiked with glucose and lactate in powder form to avoid diluting the fluid.…”