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. 2024 Feb 14:100:100736.
doi: 10.1016/j.curtheres.2024.100736. eCollection 2024.

Effects of Low-Dose Glucagon on Subcutaneous Insulin Absorption in Pigs

Ingrid Anna Teigen  1 , Marte Kierulf Åm  1 , Misbah Riaz  1   2 , Sverre Christian Christiansen  1   2 , Sven Magnus Carlsen  1   2
Affiliations

Effects of Low-Dose Glucagon on Subcutaneous Insulin Absorption in Pigs

Ingrid Anna Teigen et al. Curr Ther Res Clin Exp. .

Abstract

Background: Slow insulin absorption prevents the development of a fully automated artificial pancreas with subcutaneous insulin delivery.

Objective: We have hypothesized that glucagon could be used as a vasodilator to accelerate insulin absorption in a bihormonal subcutaneous artificial pancreas. The present proof-of-concept study is the first study to investigate the pharmacokinetics of insulin after subcutaneous administration of a low dose of glucagon at the site of subcutaneous insulin injection.

Methods: Twelve anesthetized pigs were randomized to receive a subcutaneous injection of 10 IU insulin aspart with either 100 µg glucagon or the equivalent volume of placebo (0.9% saline solution) injected at the same site. Arterial samples were collected for 180 minutes to determine insulin, glucagon, and glucose concentrations.

Results: Glucagon did not influence the insulin concentration Tmax in plasma. The plasma insulin AUC0-∞ was significantly larger after glucagon administration (P < 0.01). The glucagon group had significantly higher glucose concentrations in the first 30 minutes after insulin administration (P < 0.05).

Conclusions: This proof-of-concept study indicates that glucagon may increase the total absorption of a single dose of subcutaneously injected insulin. This is a novel observation. However, we did not observe any reduction in insulin concentration Tmax, as we had hypothesized. Further, glucagon induced a significant, undesirable increase in early blood glucose concentrations.

Keywords: Diabetes mellitus; Glucagon; Insulin; Pharmacokinetics; Type 1; cartificial pancreas.

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Conflict of interest statement

Norwegian University of Science and Technology, the university where the research was conducted and where the researchers reside, has a patent filed related to the research. S. Carlsen and S. Christiansen are among the inventors. The authors have indicated that there are no other conflicts of interest regarding the content of this article.

Figures

Fig 1
Fig. 1
Photo showing subcutaneous drug infusion on the neck of a pig. The insulin and glucagon/placebo infusions were delivered using an insertion guide (blue octagon).
Fig 2
Fig 2
Photo of skin incision after injection of methylene blue dye. Tissue deposition was investigated by injecting methylene blue dye after the pigs were humanely killed at the end of all experiments. Figure 2 illustrates unintended intramuscular injection in 1 of the placebo-treated pigs.
Fig 3
Fig 3
Mean (SD) insulin concentrations in arterial plasma over time in both study groups.
Fig 4
Fig 4
Total insulin concentrations in arterial plasma and porcine insulin concentrations in plasma in the glucagon group over time for all pigs.
Fig 5
Fig 5
Total insulin concentrations in arterial plasma and porcine insulin concentrations in plasma in the placebo group over time for all pigs.
Fig 6
Fig 6
Change in mean arterial glucose concentration (with 95% CI error bars) over time in both study groups.
See this image and copyright information in PMC

References

    1. Moon S.J., Jung I., Park C.Y. Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence. Diabetes Metab J. 2021;45(6):813–839. - PMC - PubMed
    1. Biester T., Tauschmann M., Chobot A., Kordonouri O., Danne T., Kapellen T., Dovc K. The automated pancreas: A review of technologies and clinical practice. Diabetes Obes Metab. 2022;24(Suppl 1):43–57. - PubMed
    1. Christiansen S.C., Fougner A.L., Stavdahl O., Kolle K., Ellingsen R., Carlsen S.M. A Review of the Current Challenges Associated with the Development of an Artificial Pancreas by a Double Subcutaneous Approach. Diabetes Ther. 2017;8(3):489–506. - PMC - PubMed
    1. Teigen I.A., Riaz M., Åm M.K., Christiansen S.C., Carlsen S.M. Vasodilatory effects of glucagon: A possible new approach to enhanced subcutaneous insulin absorption in artificial pancreas devices. Frontiers in Bioengineering and Biotechnology. 2022;10 - PMC - PubMed
    1. Åm M.K., Munkerud E.Y., Berge M.H., Christiansen S.C., Carlsen S.M. The effect of glucagon on local subcutaneous blood flow in non-diabetic volunteers; a proof-of-concept study. Eur J Pharmacol. 2022;926 - PubMed

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