Sir-Petermann Teresa, Angel Barbara, Maliqueo Manuel, Santos José Luis, Riesco María Virginia, Toloza Henry, Pérez-Bravo Francisco
Laboratory of Endocrinology, Department of Medicine, School of Medicine, San Juan de Dios Hospital, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile.
Nutrition. 2004 Oct;20(10):905-10. doi: 10.1016/j.nut.2004.08.017.
We evaluated metabolic parameters in Chilean women with polycystic ovary syndrome (PCOS) who were carriers and non-carriers of the glycine-to-arginine substitution at codon 972 (Gly972Arg) variant of insulin receptor substrate-1 and to assess insulin response after oral high- and low-glycemic loads
In 146 women with PCOS and 97 healthy women (HW), Gly972Arg genotypes were obtained by polymerase chain reaction, and an oral glucose tolerance test was performed with glucose and insulin measurements. An insulinogenic index, a homeostasis model assessment for insulin resistance, and whole-body insulin sensitivity index (composite) were calculated. Eight carriers and eight non-carriers (four PCOS and four HW, respectively) underwent a 50-g glucose (high glycemic) or 50-g fructose (low glycemic) load with serum glucose and insulin measurements at 15-min intervals for 3 h.
The frequency of the Gly972Arg variant was higher in PCOS patients than in HW (P < 0.05). The insulinogenic index was lower in HW carriers than in non-carriers (P < 0.05). In PCOS carriers, 2-h insulin was higher than in those without the mutation. In overweight PCOS carriers, the homeostasis model assessment for insulin resistance was higher and the insulin sensitivity index was lower than in PCOS patients without the mutation. In HW carriers, a delay in the maximal response of insulin secretion was observed, with a decrease of 26.7% in insulin concentrations 30 to 60 min after the 50-g glucose load. Glucose concentrations increased by 19.7% between 60 and 120 min. Glucose concentrations between 0 and 120 min were 14.9% higher in PCOS carriers than in non-carriers after the 50-g glucose load.
In HW, this polymorphism appears to be associated with a decrease in insulin secretion; in PCOS women, this polymorphism interacts with obesity to influence insulin resistance, thus contributing to the pathogenesis of the metabolic component of PCOS.
我们评估了智利多囊卵巢综合征（PCOS）女性的代谢参数，这些女性是胰岛素受体底物-1第972密码子甘氨酸到精氨酸替换（Gly972Arg）变体的携带者和非携带者，并评估了口服高血糖负荷和低血糖负荷后的胰岛素反应。
对146例PCOS女性和97例健康女性（HW），通过聚合酶链反应获得Gly972Arg基因型，并进行口服葡萄糖耐量试验，测量血糖和胰岛素水平。计算胰岛素生成指数、胰岛素抵抗的稳态模型评估和全身胰岛素敏感性指数（综合）。8名携带者和8名非携带者（分别为4例PCOS患者和4例HW）接受50g葡萄糖（高血糖）或50g果糖（低血糖）负荷，每隔15分钟测量一次血清葡萄糖和胰岛素水平，持续3小时。
PCOS患者中Gly972Arg变体的频率高于HW（P<0.05）。HW携带者的胰岛素生成指数低于非携带者（P<0.05）。在PCOS携带者中，2小时胰岛素水平高于无突变者。在超重的PCOS携带者中，胰岛素抵抗的稳态模型评估更高，胰岛素敏感性指数低于无突变的PCOS患者。在HW携带者中，观察到胰岛素分泌的最大反应延迟，50g葡萄糖负荷后30至60分钟胰岛素浓度下降26.7%。60至120分钟之间葡萄糖浓度增加19.7%。50g葡萄糖负荷后，0至120分钟之间PCOS携带者的葡萄糖浓度比非携带者高14.9%。
在HW中，这种多态性似乎与胰岛素分泌减少有关；在PCOS女性中，这种多态性与肥胖相互作用影响胰岛素抵抗，从而促成PCOS代谢成分的发病机制。
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