Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, Sydney, Australia; St. Vincent's Clinical School, University of NSW, Sydney, Australia.
Neuroscience Division, Garvan Institute of Medical Research, St Vincent's Hospital, Darlinghurst, Sydney, Australia.
Neuropeptides. 2021 Aug;88:102150. doi: 10.1016/j.npep.2021.102150. Epub 2021 Apr 16.
The prevalence of Type 2 diabetes increases under conditions of obesity but also due to aging. While a variety of treatment options are being explored there are still many unanswered questions about the underlying mechanisms for the aetiology and progression of this illness. Here we show that pre-treatment with Ninjin'yoeito (NYT), a herbal medicine composed of 12 different ingrediencies, before a glucose challenge results in significantly improved glucose tolerance. This occurs in the absence of significant alterations in insulin excursion compared to vehicle treatment, indicating NYT improves insulin responsiveness and/or insulin-independent glucose disposal. Furthermore, we identify Ginseng - one of the 12 ingredients of NYT - as one key component contributing to NYT's effect on glucose clearance. Importantly, lack of Y4 receptor signalling abolishes the positive effects of NYT on glucose tolerance suggesting Y4 receptor-controlled pathways are crucial in mediating this action of NYT. Using c-fos as neuronal activation marker, we show NYT activates the area postrema - a circumventricular organ in the brainstem that expresses high level of Y4 receptors, supporting an involvement of brainstem Y4 signalling in NYT-activated central networks. Together, these data suggest that NYT is a positive influencer of glucose metabolism in insulin-sensitive tissues and the mechanistic actions of NYT include brainstem Y4 circuitries.
2 型糖尿病的患病率在肥胖条件下增加，但也由于衰老。虽然正在探索各种治疗选择，但对于这种疾病的病因和进展的潜在机制仍有许多未解决的问题。在这里，我们表明，在葡萄糖挑战前用包含 12 种不同成分的草药 Ninjin'yoeito（NYT）进行预处理可显著改善葡萄糖耐量。与载体处理相比，这一过程中胰岛素波动没有明显变化，这表明 NYT 可改善胰岛素反应性和/或胰岛素非依赖性葡萄糖处置。此外，我们确定人参 - NYT 的 12 种成分之一 - 是 NYT 对葡萄糖清除作用的关键成分之一。重要的是，Y4 受体信号缺失会消除 NYT 对葡萄糖耐量的积极影响，这表明 Y4 受体控制的途径对于介导 NYT 的这种作用至关重要。使用 c-fos 作为神经元激活标记，我们表明 NYT 激活了后极区 - 脑干中的一个室周器官，其表达高水平的 Y4 受体，支持 Y4 受体控制的脑干信号通路在 NYT 激活的中枢网络中的参与。总之，这些数据表明，NYT 是胰岛素敏感组织中葡萄糖代谢的积极影响因素，NYT 的作用机制包括脑干 Y4 回路。
