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

Abstract

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

• Artificial pancreas
• Diabetes mellitus
• Glucagon
• Insulin
• Pharmacokinetics
• Type 1