Ninjin'yoeito, a herbal medicine, enhances glucose tolerance in mice

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.