INSULIN RESISTANCE WITH ACANTHOSIS NIGRICANS - THE ROLES OF OBESITY AND ANDROGEN EXCESS
INSULIN RESISTANCE WITH ACANTHOSIS NIGRICANS - THE ROLES OF OBESITY AND ANDROGEN EXCESS
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DOI：
10.1016/0026-0495(86)90201-5
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发表时间：
1986-03-01
影响因子：
9.8
通讯作者：
MEYER, WJ
中科院分区：
文献类型：
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作者：
STUART, CA;PETERS, EJ;MEYER, WJ
在对11名患有这种疾病的女性进行的研究中，评估了高雄激素血症和肥胖在伴黑棘皮病的严重胰岛素抵抗综合征中的作用。我们在这些受试者中的结果进行了比较，以雄激素过多或肥胖程度相匹配的对照受试者的评价。与正常女性相比，肥胖（OB）、高雄激素血症（HO）和黑棘皮病（AN）组的空腹胰岛素水平分别高3倍、5倍和15倍。对标准外源性胰岛素推注的反应性在OB组为正常的78%，在HO组为正常的40%，在AN组为正常的30%。胰岛素与OB组和HO组单核细胞的结合适度减少，主要是由于受体数量减少。作为一个组，AN受试者与正常或体重匹配的对照组相比，表现出单核细胞胰岛素结合的显着减少，主要是由于受体数量的减少。然而，AN组中的两名患者具有正常的胰岛素结合，这表明至少在这些受试者中的一些受试者中存在胰岛素抵抗的受体后机制。采用正葡萄糖钳夹技术测定了3例棘皮病患者体内葡萄糖利用胰岛素剂量反应曲线。所有3例受试者的曲线均右移，最大利用率降低，与胰岛素作用的受体和受体后缺陷相一致。在评价高雄激素血症、胰岛素抵抗和黑棘皮病之间的关系时，血浆胰岛素基础水平与睾酮和雄烯二酮之间存在显著相关性。此外，黑棘皮病的严重程度与高胰岛素血症的程度直接相关，与雄激素水平无关。我们的数据表明，肥胖棘皮症患者的胰岛素抵抗不能归因于高雄激素血症或肥胖，因为对照组雄激素过多的严重程度与肥胖程度相匹配，胰岛素抵抗要少得多。
The roles of hyperandrogenemia and obesity in the syndrome of severe insulin resistance with acanthosis nigricans were evaluated in studies of 11 females with this condition. Our results in these subjects were compared to evaluations of control subjects matched for degree of androgen excess or obesity. Fasting insulin levels were 3-, 5-, and 15-fold higher in the obese (OB), hyperandrogenemic (HO), and acanthosis nigricans (AN) groups, respectively, when compared to normal females. Responsiveness to a standard bolus of exogenous insulin was 78% of normal in the OB group, 40% of normal in the HO group and 30% of normal in the AN group. Insulin binding to monocytes from both the OB group, and the HO group was modestly diminished primarily due to decreased receptor number. As a group, AN subjects when compared to either normal or weight-matched controls, demonstrated a significant decrease in monocyte insulin binding predominantly due to a decrease in receptor number. However, two patients in the AN group had normal insulin binding suggesting a postreceptor mechanism for the insulin resistance in at least some of these subjects. In vivo glucose utilization insulin dose response curves were determined in 3 acanthotic subjects using the euglycemic clamp technique. All 3 of these subjects had a right shift of the curve and diminished maximal utilization, consistent with combined receptor and postreceptor defects in insulin action. In evaluating the relationship between hyperandrogenemia, insulin resistance, and acanthosis nigricans, significant correlations among basal levels of plasma insulin, and both testosterone and androstenedione were demonstrated. Further, the severity of the acanthosis nigricans was directly related to the degree of hyperinsulinemia and was not correlated to the level of androgens. Our data suggest that the insulin resistance seen in obese acanthotic subjects cannot be attributed to hyperandrogenemia or obesity, since control subjects matched for severity of androgen excess of degree of obesity had much less insulin resistance.