Glucose Activates Vagal Control of Hyperglycemia and Inflammation in Fasted Mice
Glucose Activates Vagal Control of Hyperglycemia and Inflammation in Fasted Mice
复制标题
葡萄糖激活禁食小鼠迷走神经对高血糖和炎症的控制
DOI：
10.1038/s41598-018-36298-z
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发表时间：
2019-01-30
影响因子：
4.6
通讯作者：
Ulloa, Luis
中科院分区：
文献类型：
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作者：
Joseph, Biju;Shimojo, Guilherme;Ulloa, Luis
脓毒症是住院患者的主要死亡原因。许多实验性治疗在脓毒症的临床试验中可能都失败了，部分原因是它们关注的是健康动物的免疫反应，而不是模仿脓毒症患者的代谢环境。流行病学研究表明，代谢和免疫改变之间存在关联，超过三分之一的脓毒症患者患有糖尿病，但这些系统之间的联系机制尚不清楚。在这里，我们报告了代谢禁食增加了实验性脓毒症的全身炎症和恶化的存活率。在禁食小鼠中喂食和注射葡萄糖可以激活迷走神经张力，而不会影响血压。迷走神经刺激可降低假手术小鼠的高血糖和血清肿瘤坏死因子水平，但仅能降低脾切除小鼠的高血糖。迷走神经刺激诱导肾上腺产生多巴胺。实验性糖尿病增加了实验性脓毒症的高血糖和全身炎症。非诺多巴是一种特异性的多巴胺能1型激动剂，可减轻糖尿病内毒素血症小鼠的高血糖和全身炎症。这些结果表明，葡萄糖通过多巴胺激活了对禁食脓毒症小鼠高血糖和炎症的迷走神经控制。
Sepsis is a leading cause of death in hospitalized patients. Many experimental treatments may have failed in clinical trials for sepsis, in part, because they focused on immune responses of healthy animals that did not mimic the metabolic settings of septic patients. Epidemiological studies show an association between metabolic and immune alterations and over 1/3 of septic patients are diabetic, but the mechanism linking these systems is unknown. Here, we report that metabolic fasting increased systemic inflammation and worsened survival in experimental sepsis. Feeding and administration of glucose in fasted mice activated the vagal tone without affecting blood pressure. Vagal stimulation attenuated hyperglycemia and serum TNF levels in sham but only hyperglycemia in splenectomized mice. Vagal stimulation induced the production of dopamine from the adrenal glands. Experimental diabetes increased hyperglycemia and systemic inflammation in experimental sepsis. Fenoldopam, a specific dopaminergic type-1 agonist, attenuated hyperglycemia and systemic inflammation in diabetic endotoxemic mice. These results indicate that glucose activates vagal control of hyperglycemia and inflammation in fasted septic mice via dopamine.