Jacobs M A, Salobir B, Popp-Snijders C, Ader H, Heine R J
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Diabet Med. 1997 Mar;14(3):248-57. doi: 10.1002/(SICI)1096-9136(199703)14:3<248::AID-DIA337>3.0.CO;2-0.
Lys(B28)Pro(B29) human insulin analogue (Lispro) is a newly developed monomeric insulin analogue with a rapid onset and short duration of action. The aim of the study was to compare the thresholds for the counterregulatory responses during a stepwise euglycaemic/hypoglycaemic clamp for insulin lispro (LP), human (H), and porcine (P) insulin in a randomized order in 12 healthy male volunteers (age 22.4 +/- 1.7 years, BMI 21.9 +/- 1.7 kg m-2). A euglycaemic period of 2 h was followed by three hypoglycaemic levels of 60 min each; from 150-210 min at 3.5 mmol l-1, 240-300 min at 3.0 mmol l-1 and 330-390 min at 2.5 mmol l-1. Plasma insulin levels during the 50 mU kg-1 h-1 infusions and blood glucose levels were not significantly different. The glucose requirements (mean +/- SD) during the last part of the euglycaemic period (90-120 min) tended to be higher during LP compared to those during H and P; 2239 +/- 702 and 1929 +/- 769, 1957 +/- 725 mg kg-1, P = 0.067, respectively. The thresholds (blood glucose level at which a sustained elevation of the counterregulatory hormones as compared to the mean at normoglycaemia level 4.0 mmol l-1, occurs) for the various hormones were very similar during LP, H, and P insulin infusions and occurred at 253.8 +/- 56.7, 256.3 +/- 55.3 and 257.5 +/- 70.0 min for adrenaline; 241.4 +/- 80.3, 260.5 +/- 82.5 and 225.0 +/- 75.9 min for noradrenaline; 307.5 +/- 65.5, 304.1 +/- 74.1 and 322.5 +/- 40.4 min for cortisol; 263.8 +/- 50.3, 255.0 +/- 63.6 and 249.6 +/- 50.9 min for growth hormone; 236.3 +/- 78.2, 200.0 +/- 73.1 and 226.3 +/- 65.5 for pancreatic polypeptide. The autonomic and neuroglycopenic symptoms were elicited at 240 and 300 min, respectively. In conclusion, our data indicate a tendency to a higher biological activity of approximately 10% for Lispro insulin. During a stepwise euglycaemic/hypoglycaemic clamp, the counterregulatory hormone responses to insulin lispro, human insulin, and porcine insulin were similar.
赖脯胰岛素（Lys[B28]Pro[B29]人胰岛素类似物）是一种新开发的单体胰岛素类似物，起效迅速，作用持续时间短。本研究的目的是在12名健康男性志愿者（年龄22.4±1.7岁，体重指数21.9±1.7 kg/m²）中，以随机顺序比较在逐步正常血糖/低血糖钳夹期间赖脯胰岛素（LP）、人胰岛素（H）和猪胰岛素（P）的对抗调节反应阈值。2小时的正常血糖期后，接着是三个各60分钟的低血糖水平；分别在150 - 210分钟为3.5 mmol/L，240 - 300分钟为3.0 mmol/L，330 - 390分钟为2.5 mmol/L。在50 mU/kg⁻¹ h⁻¹输注期间的血浆胰岛素水平和血糖水平无显著差异。在正常血糖期的最后部分（90 - 120分钟），与H和P相比，LP期间的葡萄糖需求量（均值±标准差）有升高趋势；分别为2239±702、1929±769、1957±725 mg/kg，P = 0.067。在输注LP、H和P胰岛素期间，各种激素的阈值（与正常血糖水平4.0 mmol/L时的均值相比，对抗调节激素持续升高时的血糖水平）非常相似，肾上腺素分别出现在253.8±56.7、256.3±55.3和257.5±70.0分钟；去甲肾上腺素分别出现在241.4±80.3、260.5±82.5和225.0±75.9分钟；皮质醇分别出现在307.5±65.5、304.1±74.1和322.5±40.4分钟；生长激素分别出现在263.8±50.3、255.0±63.6和249.6±50.9分钟；胰多肽分别出现在236.3±78.2、20·0±73.1和226.3±65.5分钟。自主神经症状和神经低血糖症状分别在240分钟和300分钟出现。总之，我们的数据表明赖脯胰岛素的生物活性有大约10%的升高趋势。在逐步正常血糖/低血糖钳夹期间，赖脯胰岛素、人胰岛素和猪胰岛素的对抗调节激素反应相似。
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