The dose-related hypoglycemic effects of insulin emulsions incorporating highly purified EPA and DHA
The dose-related hypoglycemic effects of insulin emulsions incorporating highly purified EPA and DHA
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DOI：
10.1016/s0378-5173(00)00411-7
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发表时间：
2000-05-25
影响因子：
5.8
通讯作者：
Nagai, T
中科院分区：
文献类型：
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作者：
Morishita, M;Kajita, M;Nagai, T
研究了高纯度二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)组成的胰岛素乳剂的量效关系。将含2%DHA或EPA的胰岛素剂量为0、10、25、50IU/kg的水包水型油包水型多重乳剂直接注入结肠和直肠。血清胰岛素水平升高，血糖水平下降，与胰岛素剂量相关。在直肠，胰岛素剂量与C-max或AUC(胰岛素)呈线性关系，在结肠则呈非线性关系。这一趋势在DHA中更为明显。在含有2%DI-IA的乳剂的体内直肠吸收实验中，5IU/kg的胰岛素乳剂可迅速、短暂地升高血清胰岛素水平，并显著降低血糖水平。药物利用度由S.C.剂量-反应曲线确定。胰岛素用量为43.2+/-26.3%(平均+/-S.D.)。通过乳酸脱氢酶(LDH)释放试验评价添加2%EPA或DHA的乳剂的粘膜刺激性，并与添加2%油酸或亚麻酸的乳剂进行比较。只有在肠内应用含2%油酸的乳剂时，乳酸脱氢酶才能显着释放到肠系膜静脉。我们的结果表明，含有高纯度长链多不饱和脂肪酸的乳剂，特别是DHA，有可能成为胰岛素肠内给药的制剂。(C)2000 Elsevier Science B.V.保留所有权利。
The dose-related pharmacological effects of insulin emulsion incorporating highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were investigated. Water-in-oil-in-water multiple emulsions (insulin dose, 0, 10, 25 and 50 IU/kg) incorporating 2% DHA or EPA were administered directly into the colonic and rectal loops in situ. Serum insulin levels rose and serum glucose levels decreased in an insulin dose-related fashion. The relationship of insulin dose and C-max or AUC(insulin) was linear at the rectum, but a non-linear relationship was observed at the colon. The trend was more predominant in DHA. In the in vivo rectal absorption experiment using emulsions incorporating 2% DI-IA, 5 IU/kg of insulin emulsion produced a rapid, transitory increase in serum insulin levels and strong reduction of serum glucose levels. The pharmacological availability determined from the dose-response curve by s.c. administration of insulin reached 43.2 +/- 26.3% (mean +/- S.D.). Mucosal irritation caused by administration of emulsions incorporating 2% EPA or DHA was evaluated by a lactate dehydrogenase (LDH) release study, and compared with those of the emulsion incorporating 2% oleic or linolenic acid. Only when emulsion incorporating 2% oleic acid was applied in the intestine did significant LDH release into the mesenteric veins occur. Our results indicate that emulsion incorporating highly purified long-chain polyunsaturated fatty acid, especially DHA, has the potential of becoming the formulation for enteral delivery of insulin. (C) 2000 Elsevier Science B.V. All rights reserved.