The brain is emerging as an important regulator of systemic glucose metabolism. Accumulating data from animal and observational human studies suggest that striatal dopamine signaling plays a role in glucose regulation, but direct evidence in humans is currently lacking. We present a series of experiments supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. First, we present the case of a diabetes patient who displayed strongly reduced insulin requirements after treatment with bilateral deep brain stimulation (DBS) targeting the anterior limb of the internal capsule. Next, we show that DBS in this striatal area, which induced dopamine release, increased hepatic and peripheral insulin sensitivity in 14 nondiabetic patients with obsessive-compulsive disorder. Conversely, systemic dopamine depletion reduced peripheral insulin sensitivity in healthy subjects. Supporting these human data, we demonstrate that optogenetic activation of dopamine D₁ receptor–expressing neurons in the nucleus accumbens increased glucose tolerance and insulin sensitivity in mice. Together, these findings support the hypothesis that striatal neuronal activity regulates systemic glucose metabolism.

大脑正在成为全身性葡萄糖代谢的重要调节剂。来自动物和观察性人类研究的累积数据表明，纹状体多巴胺信号传导在葡萄糖调节中起作用，但目前尚缺乏人类的直接证据。我们提出了一系列实验，通过纹状体多巴胺信号传导支持外周葡萄糖代谢的调节。首先，我们介绍了一个糖尿病患者的案例，该患者在以内囊前肢为目标的双侧深部脑刺激（DBS）治疗后显示出大大降低的胰岛素需求。接下来，我们显示了在14位非强迫症非糖尿病患者中，诱导多巴胺释放的纹状体区域DBS增加了肝和外周胰岛素敏感性。反过来，系统性多巴胺的消耗降低了健康受试者的外周胰岛素敏感性。支持这些人类数据，我们证明了多巴胺D的光遗传学激活伏隔核中表达_1个受体的神经元增加了小鼠的葡萄糖耐量和胰岛素敏感性。总之，这些发现支持了纹状体神经元活性调节全身葡萄糖代谢的假说。