Kolterman O G, Schwartz S, Corder C, Levy B, Klaff L, Peterson J, Gottlieb A
Amylin Pharmaceuticals, Inc., San Diego, CA 92121, USA.
Diabetologia. 1996 Apr;39(4):492-9. doi: 10.1007/BF00400683.
Individuals with insulin-dependent diabetes mellitus (IDDM or type 1 diabetes) are deficient in both insulin and amylin, peptides secreted by the beta cell. We have investigated the effects of amylin replacement therapy employing the human amylin analogue, pramlintide (25, 28, 29-pro-human amylin, previously referred to as AC137), upon the responses to a standardized insulin infusion (40 mU. kg-1. h-1) for 100 min and a liquid Sustacal meal (360 kcal) in 84 healthy IDDM patients. Following baseline evaluations, patients were randomly assigned to receive subcutaneous injections of placebo, 30, 100 or 300 micrograms pramlintide 30 min before meals for 14 days. There was no meaningful difference between adverse events reported by the 30-micrograms pramlintide and the placebo groups, but ten subjects withdrew due to nausea, eight of these in the 300-micrograms dose group. Peak plasma pramlintide concentrations for the 30-micrograms group were 21 +/- 3 and 29 +/- 5 pmol/l on Days 1 and 14, respectively. These values are similar to postprandial plasma amylin concentrations in normal volunteers. The plasma glucose, free insulin, glucagon, epinephrine and norepinephrine concentrations during the insulin infusion test before and after therapy were identical in each of the group. Prior to pramlintide therapy, Sustacal ingestion produced a 4.0-4.8 mmol/l rise in plasma glucose concentrations in each of the groups. Pramlintide therapy reduced postprandial hyperglycaemia as reflected by the 3-h incremental AUCglucose (AUCglucose above or below fasting glucose concentration) Day 1 vs Day 14: 30 micrograms, 322 +/- 92 vs -38 +/- 161 mmol/l.min, p = 0.010; 100 micrograms, 317 +/- 92 vs -39 +/- 76 mmol/l.min, p = 0.001; and 300 micrograms, 268 +/- 96 vs -245 +/- 189 mmol/l.min, p = 0.077. Thus, pramlintide therapy with these regimens did not appear to impair either in vivo insulin action or the counter-regulatory response to hypoglycaemia but did show a clear effect of blunting postprandial hyperglycaemia following a standardized meal.
胰岛素依赖型糖尿病（IDDM或1型糖尿病）患者缺乏胰岛素和胰岛淀粉样多肽，这两种肽均由β细胞分泌。我们研究了使用人胰岛淀粉样多肽类似物普兰林肽（25、28、29 - 脯氨酸人胰岛淀粉样多肽，以前称为AC137）进行胰岛淀粉样多肽替代疗法，对84例健康IDDM患者接受标准化胰岛素输注（40 mU·kg⁻¹·h⁻¹，持续100分钟）和液体营养配方奶（360千卡）的反应的影响。在进行基线评估后，患者被随机分配在餐前30分钟皮下注射安慰剂、30、100或300微克普兰林肽，持续14天。30微克普兰林肽组和安慰剂组报告的不良事件之间没有显著差异，但有10名受试者因恶心退出，其中8名在300微克剂量组。30微克组第1天和第14天的血浆普兰林肽峰值浓度分别为21±3和29±5 pmol/l。这些值与正常志愿者的餐后血浆胰岛淀粉样多肽浓度相似。治疗前后胰岛素输注试验期间，各治疗组的血浆葡萄糖、游离胰岛素、胰高血糖素、肾上腺素和去甲肾上腺素浓度均相同。在普兰林肽治疗前，各治疗组摄入营养配方奶后血浆葡萄糖浓度升高4.0 - 4.8 mmol/l。普兰林肽治疗可减轻餐后高血糖，这体现在第1天与第14天的3小时葡萄糖增量AUC（高于或低于空腹血糖浓度的葡萄糖AUC）：30微克组，322±92 vs -38±161 mmol/l·min，p = 0.010；100微克组，317±92 vs -39±76 mmol/l·min，p = 0.001；300微克组，268±96 vs -245±189 mmol/l·min，p = 0.077。因此，这些治疗方案的普兰林肽治疗似乎既不损害体内胰岛素作用，也不损害对低血糖的反调节反应，但确实显示出在标准化餐后减轻餐后高血糖的明显效果。
