[LYS(B28), PRO(B29)]-HUMAN INSULIN - A RAPIDLY ABSORBED ANALOG OF HUMAN INSULIN
[LYS(B28), PRO(B29)]-HUMAN INSULIN - A RAPIDLY ABSORBED ANALOG OF HUMAN INSULIN
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DOI：
10.2337/diabetes.43.3.396
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发表时间：
1994-03-01
期刊：
影响因子：
7.7
通讯作者：
WOODWORTH, JR
中科院分区：
文献类型：
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作者：
HOWEY, DC;BOWSHER, RR;WOODWORTH, JR
[Lys(B28), Pro(B29)]-人胰岛素（LYSPRO）是一种胰岛素类似物，其中b链28和29位的天然氨基酸序列是倒置的。这些变化导致胰岛素分子在溶液中自我结合的能力大大降低。这些临床研究旨在比较LYSPRO与人类皮下注射后的常规胰岛素。我们想评价添加锌对LYSPRO药代动力学和药效学的影响。此外，我们还比较了LYSPRO和人常规胰岛素皮下注射后与人常规胰岛素静脉注射后的药代动力学和药效学。因此，我们比较了四种治疗方案：无锌LYSPRO皮下注射(A)、含锌LYSPRO皮下注射(B)、人常规胰岛素皮下注射(C)和人常规胰岛素静脉注射(D)。在葡萄糖钳夹期间，我们给10名健康（非糖尿病）男性每个治疗10- u的剂量。皮下注射无锌LYSPRO后，血清胰岛素浓度峰值高出两倍以上（血清最高胰岛素水平[C-max]， 698对308 pM， A对C），在不到一半的时间内（达到C-max的时间[T-max]， 42对101 min， A对C）。与此同时，葡萄糖输注速率在大约一半的时间内达到峰值（时间到最大葡萄糖输注速率[TR(max)], 99 vs. 179 min, A vs. C），并略高于人常规胰岛素（最大葡萄糖输注速率[R(max)], 3.1 vs. 2.2 mmol/min, A vs. C）。虽然锌的加入稍微延缓了LYSPRO的吸收（C-max, 550 vs. 698 pM, B vs. A），但含锌的LYSPRO保持了其独特的特征（T-max, 53 vs. 42 min, B vs. A）。LYSPRO皮下注射的药效学作用比普通胰岛素快。
[Lys(B28), Pro(B29)]-human insulin (LYSPRO) is an insulin analogue in which the natural amino acid sequence of the B-chain at positions 28 and 29 is inverted. These changes result in an insulin molecule with a greatly reduced capacity for self-association in solution. These clinical studies were designed to compare LYSPRO with human Regular insulin after subcutaneous injection in humans. We wanted to evaluate the effect of adding zinc to LYSPRO on its pharmacokinetics and pharmacodynamics. In addition, we compared the pharmacokinetics and pharmacodynamics of LYSPRO and human Regular insulin after subcutaneous injection to those of human Regular insulin given intravenously. Thus, we compared four treatments: solutions of zinc-free LYSPRO given subcutaneously (A), zinc-containing LYSPRO given subcutaneously (B), human Regular insulin given subcutaneously (C), and human Regular insulin given intravenously (D). We gave a 10-U dose of each treatment to 10 healthy (nondiabetic) men during glucose clamps. Serum insulin concentrations peaked more than two times higher (maximum serum insulin level [C-max], 698 vs. 308 pM, A vs. C) and in less than half the time (time to C-max [T-max], 42 vs. 101 min, A vs. C) after subcutaneous injection of zinc-free LYSPRO. At the same time, the glucose infusion rate peaked in about half the time (time to maximum glucose infusion rate [TR(max)], 99 vs. 179 min, A vs. C) and was slightly but not significantly higher (maximum glucose infusion rate [R(max)], 3.1 vs. 2.2 mmol/min, A vs. C) than that of human Regular insulin. Although the addition of zinc retarded the absorption of LYSPRO slightly (C-max, 550 vs. 698 pM, B vs. A), zinc-containing LYSPRO retained its distinct profile (T-max, 53 vs. 42 min, B vs. A). LYSPRO displays faster pharmacodynamic action than human Regular insulin when injected subcutaneously.