Diamond M P, Grainger D A, Laudano A J, Starick-Zych K, DeFronzo R A
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Clin Endocrinol Metab. 1991 Apr;72(4):883-7. doi: 10.1210/jcem-72-4-883.
Extreme pharmacological elevation of the circulating insulin level acutely lowers dehydroepiandrosterone sulfate (DHEAS) levels. To assess whether more physiological elevations in plasma insulin (due to exogenous infusion or endogenous secretion) would have similar effects, we examined the levels of DHEAS, androstenedione, testosterone, and free testosterone before and after euglycemic hyperinsulinemic and hyperglycemic hyperinsulinemic clamp studies. Studies were performed in women within 20% of ideal body weight after an overnight fast. Androgen levels were measured before and at the conclusion of studies in which either insulin was infused exogenously at 1 mU/kg.min or endogenous insulin secretion was stimulated for 2 h by elevation of the plasma glucose concentration by 125 mg/dL above basal levels by an exogenous glucose infusion. Basal plasma DHEAS (6.2 +/- 0.5 mumol/L) declined to 5.2 +/- 0.4 mumol/L (P less than 0.001) during the euglycemic insulin clamp, without any significant change in testosterone, free testosterone, or androstenedione. During the hyperglycemic clamp, DHEAS fell from 6.7 +/- 0.5 to 5.1 +/- 0.4 mumol/L (P less than 0.001) in response to endogenous hyperinsulinemia; plasma testosterone, free testosterone, and androstenedione did not change significantly. There was no correlation between the elevation in plasma insulin concentration and the fall in DHEAS during either the euglycemic or hyperglycemic clamps. However, the magnitude of fall of DHEAS was directly correlated with the initial DHEAS level in both the euglycemic (r = 0.51; P less than 0.05) and hyperglycemic (r = 0.75; P less than 0.01) studies. This association of hyperinsulinemia with a reduction of circulating levels of DHEAS, but not other C-19 steroids (e.g. testosterone and androstenedione) may reflect differential mechanisms by which DHEAS levels are regulated and suggests that insulin either inhibits its biosynthesis and/or secretion, or enhances its MCR.
循环胰岛素水平的极度药理学升高会使硫酸脱氢表雄酮（DHEAS）水平急剧下降。为了评估血浆胰岛素更生理性的升高（由于外源性输注或内源性分泌）是否会产生类似影响，我们在正常血糖高胰岛素钳夹试验和高血糖高胰岛素钳夹试验前后检测了DHEAS、雄烯二酮、睾酮和游离睾酮的水平。研究在过夜禁食后体重在理想体重20%以内的女性中进行。在研究开始前及结束时测量雄激素水平，这些研究中，要么以1 mU/kg·min的速度外源性输注胰岛素，要么通过外源性葡萄糖输注使血浆葡萄糖浓度比基础水平升高125 mg/dL来刺激内源性胰岛素分泌2小时。在正常血糖胰岛素钳夹试验期间，基础血浆DHEAS（6.2±0.5 μmol/L）降至5.2±0.4 μmol/L（P<0.001），而睾酮、游离睾酮或雄烯二酮无显著变化。在高血糖钳夹试验期间，由于内源性高胰岛素血症，DHEAS从6.7±0.5降至5.1±0.4 μmol/L（P<0.001）；血浆睾酮、游离睾酮和雄烯二酮无显著变化。在正常血糖或高血糖钳夹试验期间，血浆胰岛素浓度的升高与DHEAS的下降之间均无相关性。然而，在正常血糖（r = 0.51；P<0.05）和高血糖（r = 0.75；P<0.01）研究中，DHEAS的下降幅度均与初始DHEAS水平直接相关。高胰岛素血症与循环DHEAS水平降低相关，但与其他C-19类固醇（如睾酮和雄烯二酮）无关，这可能反映了DHEAS水平调节的不同机制，并提示胰岛素要么抑制其生物合成和/或分泌，要么增强其代谢清除率。
