Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys
Timing of prenatal androgen excess determines differential impairment in insulin secretion and action in adult female rhesus monkeys
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DOI：
10.1210/jc.85.3.1206
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发表时间：
2000-03-01
影响因子：
5.8
通讯作者：
Abbott, DH
中科院分区：
文献类型：
--
作者：
Eisner, JR;Dumesic, DA;Abbott, DH
这项研究确定了孕期雄激素过多是否会导致成年雌性恒河猴胰岛素-葡萄糖稳态的不同程度的损害。10只雌性恒河猴在孕40天开始暴露于丙酸睾丸酮(早期治疗)，9只雌性恒河猴在妊娠100-115天开始暴露于丙酸睾丸酮(晚期治疗)，以及15只对照雌性恒河猴。修改后的最小模型被用来检验来自静脉葡萄糖耐量试验的各种测量，并对这些变量与体重指数之间进行回归分析。此外，还检验了倾向指数(DI)和胰岛素敏感性(S-I)与急性胰岛素抵抗之间的双曲线关系。早期接受治疗的女性表现出胰岛β细胞功能受损，表现为DI减少和S-I与葡萄糖急性胰岛素反应之间的双曲关系的百分位数排名下降。相比之下，接受晚期治疗的女性不仅表现出DI的增加，而且身体质量指数与S-I呈负相关。这些结果表明，雌性恒河猴出生前雄激素过量，无论怀孕时间如何，都会扰乱胰岛素-葡萄糖代谢动力学，妊娠早期和晚期的雄激素过剩分别会损害胰岛β细胞功能和改变胰岛素敏感性。
This study determined whether timing of prenatal androgen excess resulted in differential impairment of insulin-glucose homeostasis in adult female rhesus monkeys. Ten female rhesus monkeys exposed to testosterone propionate starting on gestational day 40 (early treated), 9 females exposed to testosterone propionate starting between gestational days 100-115 (late treated), and 15 control females were studied. The modified minimal model was used to examine various measures derived from an iv glucose tolerance test, with regression analysis performed between these variables and body mass index. In addition, the disposition index (DI) and the hyperbolic relationship between insulin sensitivity (S-I) and acute insulin response to glucose were examined. Early treated females demonstrated impaired pancreatic beta-cell function, as shown by diminished DI and decreased percentile ranking for the hyperbolic relationship between S-I and acute insulin response to glucose. In contrast, late treated females exhibited both an increase in DI and a negative relationship between body mass index and S-I. These results suggest that prenatal androgen excess in female rhesus monkeys, regardless of gestational timing, perturbs insulin-glucose homeodynamics, with androgen excess in early and late gestation impairing pancreatic beta-cell function and altering insulin sensitivity, respectively.