Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Cell Metab. 2010 Sep 8;12(3):295-305. doi: 10.1016/j.cmet.2010.06.010.
Obesity is associated with insulin resistance in metabolic tissues such as adipose, liver, and muscle, but it is unclear whether nonclassical target tissues, such as those of the reproductive axis, are also insulin resistant. To determine if the reproductive axis maintains insulin sensitivity in obesity in vivo, murine models of diet-induced obesity (DIO) with and without intact insulin signaling in pituitary gonadotrophs were created. Diet-induced obese wild-type female mice (WT DIO) were infertile and experienced a robust increase in luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) or insulin stimulation. By contrast, both lean and obese mice with a pituitary-specific knockout of the insulin receptor (PitIRKO) exhibited reproductive competency, indicating that insulin signaling in the pituitary is required for the reproductive impairment seen in DIO and that the gonadotroph maintains insulin sensitivity in a setting of peripheral insulin resistance.
肥胖与代谢组织（如脂肪、肝脏和肌肉）中的胰岛素抵抗有关，但尚不清楚非经典靶组织（如生殖轴）是否也存在胰岛素抵抗。为了确定生殖轴在肥胖症中是否保持胰岛素敏感性，在具有和不具有完整胰岛素信号的情况下创建了饮食诱导肥胖（DIO）的小鼠模型。饮食诱导肥胖的野生型雌性小鼠（WT DIO）不孕，并在促性腺激素释放激素（GnRH）或胰岛素刺激后经历了黄体生成素（LH）的强烈增加。相比之下，具有垂体特异性胰岛素受体（PitIRKO）敲除的瘦鼠和肥胖鼠都表现出生殖能力，这表明垂体中的胰岛素信号对于 DIO 中观察到的生殖障碍是必需的，并且在周围胰岛素抵抗的情况下，促性腺激素维持胰岛素敏感性。
