Lymphatic absorption is a significant contributor to the subcutaneous bioavailability of insulin in a sheep model
Lymphatic absorption is a significant contributor to the subcutaneous bioavailability of insulin in a sheep model
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DOI：
10.1023/a:1013046918190
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发表时间：
2001-11-01
影响因子：
3.7
通讯作者：
Porter, CJH
中科院分区：
文献类型：
--
作者：
Charman, SA;McLennan, DN;Porter, CJH
目的.本研究使用绵羊模型来探索皮下（SC）给药后外周淋巴细胞在胰岛素吸收中的作用，该模型允许连续收集外周淋巴细胞并同时评估全身生物利用度。在平行组设计中，可溶性人胰岛素（0.5 IU/ kg）通过皮下推注给药至未插管对照绵羊后腿的趾间间隙，和羊，其中传出腘淋巴管插管。另一组接受静脉推注（0.15 IU/kg）。从所有动物中采集血样，并在给药后12 h内连续采集淋巴液。用ELISA法测定血清胰岛素含量。对照绵羊中胰岛素的SC生物利用度为31.5 +/-3.2%，显著高于连续采集外周淋巴液时的生物利用度（18.4 +/- 1.7%）。在淋巴管插管动物中，外周淋巴中收集了17.3 +/- 1.0%的剂量。结论.基于区域淋巴中胰岛素的直接测量和连续收集区域淋巴时全身生物利用度的降低，结果表明淋巴吸收对绵羊SC给药后的总体胰岛素生物利用度有显著贡献。
Purpose. This study was conducted to explore the role of the peripheral lymphatics in insulin absorption following subcutaneous (SC) administration using a sheep model that allows continuous collection of peripheral lymph and simultaneous assessment of systemic bioavailability.Methods: In a parallel group design, soluble human insulin (0.5 IU/ kg) was administered by bolus SC injection into the interdigital space of the hind leg of non-cannulated control sheep, and sheep in which the efferent popliteal lymph duct was cannulated. A separate group received a bolus IV injection (0.15 IU/kg). Blood was sampled from all animals, and lymph was collected continuously over 12 h postdosing. Samples were assayed for insulin by ELISA.Results. The SC bioavailability of insulin in control sheep was 31.5 +/- 3.2%, which was significantly higher than when the peripheral lymph was continuously collected (18.4 +/- 1.7%). In the lymph-cannulated animals, 17.3 +/- 1.0% of the dose was collected in peripheral lymph. Conclusions. Based on the direct measurement of insulin in regional lymph and on the decrease in the systemic bioavailability when rea gional lymph was continuously collected, the results demonstrate that lymphatic absorption contributed significantly to the overall insulin bioavailability following SC administration to sheep.