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

Autor: Teigen IA; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Åm MK; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway., Riaz M; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Endocrinology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway., Christiansen SC; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Endocrinology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway., Carlsen SM; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Endocrinology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
Jazyk: angličtina
Zdroj: Current therapeutic research, clinical and experimental [Curr Ther Res Clin Exp] 2024 Feb 14; Vol. 100, pp. 100736. Date of Electronic Publication: 2024 Feb 14 (Print Publication: 2024).
DOI: 10.1016/j.curtheres.2024.100736
Abstrakt: 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 T max in plasma. The plasma insulin AUC 0-∞ 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 T max , as we had hypothesized. Further, glucagon induced a significant, undesirable increase in early blood glucose concentrations.
Competing Interests: 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.
(© 2024 Published by Elsevier Inc.)
Databáze: MEDLINE
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