小剂量胰高血糖素对猪皮下胰岛素吸收的影响

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
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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引用次数: 0

摘要

背景胰岛素吸收缓慢阻碍了皮下注射胰岛素的全自动人工胰腺的发展。目的我们假设胰高血糖素可用作血管扩张剂,以加速双激素皮下人工胰腺的胰岛素吸收。本概念验证研究是首次研究在皮下注射胰岛素部位皮下注射低剂量胰高血糖素后的胰岛素药代动力学。方法12头麻醉猪被随机分配到皮下注射10 IU天冬胰岛素,并在同一部位注射100微克胰高血糖素或等量的安慰剂(0.9%生理盐水)。结果胰高血糖素不会影响血浆中的胰岛素浓度Tmax。胰高血糖素给药后,血浆胰岛素 AUC0-∞ 显著增大(P < 0.01)。结论这项概念验证研究表明,胰高血糖素可增加单剂量皮下注射胰岛素的总吸收。这是一项新发现。然而,我们并未观察到胰岛素浓度 Tmax 有任何降低,这与我们的假设不符。此外,胰高血糖素会导致早期血糖浓度显著升高,这种情况并不理想。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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来源期刊
CiteScore
3.50
自引率
0.00%
发文量
31
审稿时长
3 months
期刊介绍: We also encourage the submission of manuscripts presenting preclinical and very preliminary research that may stimulate further investigation of potentially relevant findings, as well as in-depth review articles on specific therapies or disease states, and applied health delivery or pharmacoeconomics. CTR encourages and supports the submission of manuscripts describing: • Interventions designed to understand or improve human health, disease treatment or disease prevention; • Studies that focus on problems that are uncommon in resource-rich countries; • Research that is "under-published" because of limited access to monetary resources such as English language support and Open Access fees (CTR offers deeply discounted English language editing); • Republication of articles previously published in non-English journals (eg, evidence-based guidelines) which could be useful if translated into English; • Preclinical and clinical product development studies that are not pursued for further investigation based upon early phase results.
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