Ingrid Anna Teigen M.D., Ph.D. , Marte Kierulf Åm Ph.D. , Misbah Riaz M.D. , Sverre Christian Christiansen M.D., Ph.D. , Sven Magnus Carlsen M.D., Ph.D.
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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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>Glucagon did not influence the insulin concentration T<sub>max</sub> in plasma. The plasma insulin AUC<sub>0–∞</sub> was significantly larger after glucagon administration (<em>P</em> < 0.01). The glucagon group had significantly higher glucose concentrations in the first 30 minutes after insulin administration (<em>P</em> < 0.05).</p></div><div><h3>Conclusions</h3><p>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<sub>max</sub>, as we had hypothesized. Further, glucagon induced a significant, undesirable increase in early blood glucose concentrations.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"100 ","pages":"Article 100736"},"PeriodicalIF":1.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X24000067/pdfft?md5=c0b24e6ee8160e4af109627f08fc13fb&pid=1-s2.0-S0011393X24000067-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Effects of Low-Dose Glucagon on Subcutaneous Insulin Absorption in Pigs\",\"authors\":\"Ingrid Anna Teigen M.D., Ph.D. , Marte Kierulf Åm Ph.D. , Misbah Riaz M.D. , Sverre Christian Christiansen M.D., Ph.D. , Sven Magnus Carlsen M.D., Ph.D.\",\"doi\":\"10.1016/j.curtheres.2024.100736\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Slow insulin absorption prevents the development of a fully automated artificial pancreas with subcutaneous insulin delivery.</p></div><div><h3>Objective</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>Glucagon did not influence the insulin concentration T<sub>max</sub> in plasma. The plasma insulin AUC<sub>0–∞</sub> was significantly larger after glucagon administration (<em>P</em> < 0.01). The glucagon group had significantly higher glucose concentrations in the first 30 minutes after insulin administration (<em>P</em> < 0.05).</p></div><div><h3>Conclusions</h3><p>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<sub>max</sub>, as we had hypothesized. 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Effects of Low-Dose Glucagon on Subcutaneous Insulin Absorption in Pigs
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.
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