Role of histidine in glucose metabolism

我们之前发现，肝脏STAT3降低肝脏糖异生酶的表达，抑制肝脏葡萄糖的产生。在这里，我们发现蛋白质摄入引起的血浆组氨酸增加导致肝脏STAT3激活。静脉注射和脑室注射组氨酸也能激活肝STAT3，增强胰岛素对肝葡萄糖生成的抑制。组氨酸对肝糖生成的抑制作用可通过抑制中枢神经系统的组胺h1受体而被阻断。因此，组氨酸激活肝STAT3并通过中枢组胺作用抑制肝葡萄糖的产生。在中枢神经系统中，组氨酸和胰岛素的作用机制是独立的，但对肝糖的产生有加性的抑制作用。这表明中枢组氨酸介导的对肝糖生成的抑制作用是治疗2型糖尿病的潜在靶点。

We previously revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses hepatic glucose production. Here, we show that increased plasma histidine caused by protein intake resulted in hepatic STAT3 activation. Intravenous and intracerebroventricular administration of histidine also activated hepatic STAT3 and augmented the suppression of hepatic glucose production by insulin. Inhibition of hepatic glucose production by histidine was blocked by inhibiting histamine H1receptors in the central nervous system. Therefore, histidine activates hepatic STAT3 and suppresses hepatic glucose production via central histamine action. In the central nervous system, the mechanisms of histidine and insulin are independent, but have additive inhibitory effects on hepatic glucose prodcution. This suggests that central histidine-mediated suppressive action on hepatic glucose production is a potential target for the treatment of type 2 diabetes.