General Electric (GE) Research, 1 Research Circle, Niskayuna, NY, USA.
University of California, Los Angeles, Los Angeles, CA, USA.
Nat Biomed Eng. 2022 Jun;6(6):683-705. doi: 10.1038/s41551-022-00870-w. Epub 2022 Mar 31.
Peripheral neurons that sense glucose relay signals of glucose availability to integrative clusters of neurons in the brain. However, the roles of such signalling pathways in the maintenance of glucose homoeostasis and their contribution to disease are unknown. Here we show that the selective activation of the nerve plexus of the hepatic portal system via peripheral focused ultrasound stimulation (pFUS) improves glucose homoeostasis in mice and rats with insulin-resistant diabetes and in swine subject to hyperinsulinemic-euglycaemic clamps. pFUS modulated the activity of sensory projections to the hypothalamus, altered the concentrations of metabolism-regulating neurotransmitters, and enhanced glucose tolerance and utilization in the three species, whereas physical transection or chemical blocking of the liver-brain nerve pathway abolished the effect of pFUS on glucose tolerance. Longitudinal multi-omic profiling of metabolic tissues from the treated animals confirmed pFUS-induced modifications of key metabolic functions in liver, pancreas, muscle, adipose, kidney and intestinal tissues. Non-invasive ultrasound activation of afferent autonomic nerves may represent a non-pharmacologic therapy for the restoration of glucose homoeostasis in type-2 diabetes and other metabolic diseases.
外周神经元感知葡萄糖，并将葡萄糖可用性的信号传递给大脑中整合神经元簇。然而，这种信号通路在维持葡萄糖稳态中的作用及其对疾病的贡献尚不清楚。本文中，作者研究表明，通过外周聚焦超声刺激（pFUS）选择性激活肝门静脉系统的神经丛，可以改善胰岛素抵抗型糖尿病小鼠和大鼠以及高胰岛素-正常血糖钳夹猪的葡萄糖稳态。pFUS 调节了向下丘脑的感觉投射的活性，改变了代谢调节神经递质的浓度，并增强了这三种物种的葡萄糖耐量和利用率，而肝脑神经通路的物理横断或化学阻断消除了 pFUS 对葡萄糖耐量的影响。来自治疗动物的代谢组织的纵向多组学分析证实了 pFUS 诱导的肝脏、胰腺、肌肉、脂肪、肾脏和肠道组织中关键代谢功能的改变。自主神经传入的非侵入性超声激活可能代表一种非药物治疗方法，可用于恢复 2 型糖尿病和其他代谢疾病的葡萄糖稳态。
