Background and Aims

Glucagon has received renewed interest, particularly in the development of a dual hormone artificial pancreas (AP). Slow subcutaneous (SC) dynamics motivates for exploration of the intraperitoneal (IP) space both for glucose sensing and hormone delivery. We previously investigated IP glucagon delivery in rats [1]. Now we compared glucose dynamics after IP and SC glucagon delivery in a swine model.

Methods

Ten anaesthetized, non-diabetic, somatostatin-analogue treated pigs (35–50 kg) were, in random order, given glucagon boluses of 0.6 µg/kg IP, 0.3 µg/kg IP, and 0.6 µg/kg SC. At last, 1 mg IP glucagon was given to test maximum glucose response.

Results

Only 17 of 28 IP boluses and nine of 10 SC boluses had a glucose increasing effect. We believe this is due to prolonged fasting causing depletion of hepatic glycogen. Hence, we excluded four pigs from further analysis. The mean maximum effect on glucose for the remaining six pigs was 2.4, 2.2 and 1.6 mmol/L for 0.6 µg/kg IP, 0.3 µg/kg IP and 0.6 µg/kg SC glucagon, respectively.

Glucose increase after 14 to 30 minutes was significantly larger for the 0.6 µg/kg IP bolus compared to the equally sized SC bolus. In some pigs, a marked “first-pass-effect” is observed after IP glucagon.

Conclusions

Results indicates that adequate glucose responses by IP glucagon is achieved by smaller doses, potentially avoiding side effects of glucagon treatment by resembling physiologic glucagon secretion and distribution [2].

Further data on glucagon levels in blood following the different boluses will be presented.

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