Kotzmann H, Linkesch M, Ludvik B, Clodi M, Luger A, Schernthaner G, Prager R, Klauser R
Department of Medicine III, University of Vienna, Austria.
Eur J Clin Invest. 1995 Dec;25(12):942-7. doi: 10.1111/j.1365-2362.1995.tb01971.x.
It has been shown that danazol (14-ethinyltestosterone) induces hyperglucagonaemia. To investigate the effect of chronic glucagon excess on carbohydrate metabolism, we studied six patients before and after treatment with danazol for immunothrombopenia. Glucose tolerance and insulin, C-peptide and glucagon secretion during an oral glucose tolerance test (oGTT) as well as peripheral and hepatic insulin sensitivity were determined by means of euglycaemic clamp technique (40 mU m-2 min-1) before and after 3 months of danazol therapy. Overall glucose turnover (Rd) was assessed radioisotopically. (1) Plasma glucagon levels rose significantly from 88 +/- 16 pg mL-1 before to 683 +/- 148 pg mL-1 after therapy (P < 0.01). (2) Glucose levels during an oGTT were not significantly different before and after therapy. Glucose-stimulated insulin secretion at 60 and 120 min and the area under the curve (AUC) for insulin during the oGTT, were significantly increased after danazol treatment compared with pre-treatment values (P < 0.05), whereas glucagon secretion showed a similar decrease at both time points of investigation (NS). (3) Rd during steady state showed a significant decrease during the entire period of euglycaemic clamp following therapy (after 240 min, 3.8 +/- 0.6 vs. 5.3 +/- 0.7 mg kg-1 min-1, P < 0.05). The decline in glucagon during the clamp was similar during steady state before and after therapy. (4) Basal hepatic glucose output did not differ significantly before and after therapy (1.74 +/- 0.41 vs. 1.45 +/- 0.22 mg kg-1, NS), whereas hepatic glucose output during the clamp was significantly less suppressed after danazol therapy. The authors conclude that chronic glucagon excess leads to a decrease in peripheral and hepatic insulin action which is accompanied by an increase in insulin secretion.
已表明达那唑（14-乙炔睾酮）可诱发高胰高血糖素血症。为研究慢性胰高血糖素过量对碳水化合物代谢的影响，我们对6例免疫性血小板减少症患者在接受达那唑治疗前后进行了研究。通过正常血糖钳夹技术（40 mU m-2 min-1）在达那唑治疗3个月前后测定口服葡萄糖耐量试验（oGTT）期间的葡萄糖耐量以及胰岛素、C肽和胰高血糖素分泌，同时测定外周和肝脏胰岛素敏感性。通过放射性同位素评估总体葡萄糖周转率（Rd）。（1）血浆胰高血糖素水平从治疗前的88±16 pg mL-1显著升至治疗后的683±148 pg mL-1（P<0.01）。（2）oGTT期间的血糖水平在治疗前后无显著差异。与治疗前相比，达那唑治疗后oGTT期间60和120分钟时葡萄糖刺激的胰岛素分泌以及胰岛素曲线下面积（AUC）显著增加（P<0.05），而在两个研究时间点胰高血糖素分泌均有类似下降（无显著性差异）。（3）治疗后在整个正常血糖钳夹期间稳态时的Rd显著下降（240分钟后，3.8±0.6 vs. 5.3±0.7 mg kg-1 min-1，P<0.05）。钳夹期间胰高血糖素的下降在治疗前后稳态时相似。（4）治疗前后基础肝脏葡萄糖输出无显著差异（1.74±0.41 vs. 1.45±0.22 mg kg-1，无显著性差异），而达那唑治疗后钳夹期间肝脏葡萄糖输出的抑制作用显著减弱。作者得出结论，慢性胰高血糖素过量导致外周和肝脏胰岛素作用降低，同时伴有胰岛素分泌增加。
