Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men
Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men
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DOI：
10.1210/jc.2004-2190
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发表时间：
2005-05-01
影响因子：
5.8
通讯作者：
Hayes, FJ
中科院分区：
文献类型：
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作者：
Pitteloud, N;Hardin, M;Hayes, FJ
胰岛素抵抗与男性的低睾酮（T）水平有关，其机制尚不清楚。因此，本研究的目的是评估下丘脑-垂体-性腺轴的男性与频谱的胰岛素敏感性。21名男性（年龄25 - 65岁）进行了葡萄糖耐量试验，并使用高胰岛素-正常血糖钳夹法评估了胰岛素敏感性。胰岛素敏感性，表示为M值（毫克/千克（-1）/分钟（-1）），由钳夹最后30分钟期间的葡萄糖处置速率计算。18例受试者每10分钟采集一次血样，持续12小时，以评估LH脉动性。然后用GnRH拮抗剂诱导性腺功能减退症，然后用GnRH（750 ng/kg，iv）和人绒毛膜促性腺激素（hCG; 1000 IU，im）进行序贯刺激试验，以分别评估垂体和睾丸的反应性。9例受试者葡萄糖耐量正常，9例葡萄糖耐量受损，3例糖尿病。M与T水平呈正相关（r = 0.46; P < 0.05）。未发现M与LH分泌参数（包括平均LH水平、LH脉冲幅度、LH脉冲频率和LH对外源性GnRH给药的反应）之间存在相关性。与此相反，在M和对hCG的T反应之间观察到强相关性（r = 0.73; P < 0.005）。基线T水平与hCG治疗后T水平升高相关（r = 0.47; P < 0.05）。在钳夹过程中，T水平在最后30分钟内从基线水平367 +/- 30增加到419 +/- 38 ng/dl（P < 0.05）。从这些数据中，我们得出结论，胰岛素抵抗与男性睾丸间质细胞T分泌减少有关。需要进一步的研究来确定这种影响的机制。
Insulin resistance is associated with low testosterone ( T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men ( aged 25 - 65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value ( milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH ( 750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels ( r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG ( r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration ( r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min ( P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.