Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland
Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland.
Diabetes. 2016 Jan;65(1):34-43. doi: 10.2337/db15-0973. Epub 2015 Oct 15.
Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was blunted in GLP-1R kd rats, suggesting that VAN GLP-1Rs are physiological contributors to the neuroincretin effect after a meal. Collectively, our results highlight a crucial role for the VANs in mediating the effects of endogenous GLP-1 on food intake and glycemia and may promote the further development of GLP-1-based therapies.
营养刺激肠内分泌 L 细胞会诱导肠促胰岛素和饱腹感肽胰高血糖素样肽 1（GLP-1）的释放。迷走神经支配内脏器官，可能有助于调节肠道来源的 GLP-1 对食物摄入、能量平衡和血糖控制的影响。为了检验迷走神经传入神经元（VAN）GLP-1 受体（GLP-1R）对于内源性 GLP-1 这些作用是否必要的假说，我们建立了一种新的双侧结状神经节注射技术，以递送电病毒载体并敲低雄性 Sprague Dawley 大鼠的 VAN GLP-1R。我们发现，VAN GLP-1R 的完全表达对于正常进食条件下的长期能量平衡的维持并非必需。然而，VAN GLP-1R 敲低（kd）确实增加了进餐量并加速了胃排空。此外，GLP-1R kd 大鼠的餐后血糖升高，胰岛素释放减弱，这表明 VAN GLP-1R 是餐后神经肠促胰岛素作用的生理贡献者。总之，我们的结果强调了 VAN 在介导内源性 GLP-1 对食物摄入和血糖的影响方面的关键作用，并可能促进基于 GLP-1 的治疗方法的进一步发展。
