Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans
Effects of a novel glucagon receptor antagonist (Bay 27-9955) on glucagon-stimulated glucose production in humans
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DOI：
10.1007/s001250100006
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发表时间：
2001-11-01
期刊：
影响因子：
8.2
通讯作者：
Sullivan, JT
中科院分区：
文献类型：
--
作者：
Petersen, KF;Sullivan, JT
目的/假说。研究一种特异性胰高血糖素受体拮抗剂（Bay 27-9955）对高血糖素血症患者血浆葡萄糖浓度和葡萄糖生成率的影响。方法。该研究采用双剂量[低剂量Bay 27-9955 70 mg， （n = 6），高剂量Bay 27-9955 200 mg， （n = 8）]，双盲，安慰剂对照，交叉研究。在用[6,6-(2)H]禁食过夜后测量基础葡萄糖产量。第0分钟给予Bay 27-9955或安慰剂，第120分钟输注生长抑素[0.1杯]。(公斤。Min)(-1)]，胰岛素[24 pmol。(m(2)。Min)(-1)]和胰高血糖素[3 ng]。(公斤。min)(-1)]被初始化。基础血浆葡萄糖浓度约为5 mmol/l，基础葡萄糖生成率约为13 mmol/l。(公斤。分钟)(1)。在高胰高血糖素血症期间，血浆胰高血糖素浓度增加一倍至100 pg/ml，血浆葡萄糖浓度增加75%，达到约10 mmol/l的峰值，葡萄糖产量增加一倍至约23 mu mol。(公斤。Min)(-1) （p < 0.0001 vs基础）。在高剂量组，胰高血糖素的这些作用明显减弱，血浆葡萄糖浓度为7.6 +/- 1.1 mmol/l （p = 0.012 vs安慰剂），葡萄糖生成率最低增加到15.3 +/- 1.9 mol。（kg-min）（-1） （p < 0.0003 vs安慰剂）。在低剂量组，Bay 27-9955对这些参数的影响呈比例降低。Bay 27-9955是一种安全有效的人体胰高血糖素拮抗剂。鉴于胰高血糖素在II型（非胰岛素依赖型）糖尿病患者中增加葡萄糖生成和糖异生的潜在重要作用，这种药物可能代表了一类创新的治疗疾病的药物。
Aims/hypothesis. To study the effects of a specific glucagon receptor antagonist (Bay 27-9955), on plasma glucose concentrations and rates of glucose production in response to hyperglucagonaemia in humans. Methods. The study was conducted as a two-dose [Low Dose Bay 27-9955 70 mg, (n = 6), High Dose Bay 27-9955 200 mg, (n = 8)], double blind, placebo controlled, crossover study. Basal glucose production was measured after an overnight fast with [6,6-(2) H]. At 0 min Bay 27-9955 or placebo was administered and at 120 min an infusion of somatostatin [0.1 mug . (kg . min)(-1)], insulin [24 pmol . (m(2) . min)(-1)] and glucagon [3 ng . (kg . min)(-1)] was initiated.Results. Basal plasma glucose concentrations were about 5 mmol/l and basal rates of glucose production were about 13 mu mol . (kg . min)(-1). During the hyperglucagonaemic period, plasma glucagon concentrations doubled to 100 pg/ml, plasma glucose concentration increased by 75 % to a peak of about 10 mmol/l and glucose production doubled to about 23 mu mol . (kg . min)(-1) (p < 0.0001 vs basal). In the High Dose Group these effects of glucagon were markedly blunted, plasma glucose concentrations were 7.6 +/- 1.1 mmol/l (p = 0.012 vs placebo) and rates of glucose production increased minimally to 15.3 +/- 1.9 mol . (kg-min)(-1) (p < 0.0003 vs placebo]. In the Low Dose Group, there was a proportional decrease in the effects of Bay 27-9955 on these parameters.Conclusion/interpretation. Bay 27-9955 is an effective and safe glucagon antagonist in humans. Given the potentially important role of glucagon in increasing glucose production and gluconeogenesis in patients with Type II (non-insulin-dependent) diabetes mellitus this agent could represent an innovative class of therapeutic agents for the disease.