Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA.
Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA.
Endocrinology. 2021 Apr 1;162(4). doi: 10.1210/endocr/bqab021.
Fibroblast growth factor 19 (FGF19) is a protein hormone that produces antidiabetic effects when administered intracerebroventricularly in the forebrain. However, no studies have examined how FGF19 affects hindbrain neurons that participate directly in autonomic control of systemic glucose regulation. Within the dorsal hindbrain, parasympathetic motor neurons of the dorsal motor nucleus of the vagus (DMV) express fibroblast growth factor receptors and their activity regulates visceral homeostatic processes, including energy balance. This study tested the hypothesis that FGF19 acts in the hindbrain to alter DMV neuron excitability and lower blood glucose concentration. Fourth ventricle administration of FGF19 produced no effect on blood glucose concentration in control mice, but induced a significant, peripheral muscarinic receptor-dependent decrease in systemic hyperglycemia for up to 12 h in streptozotocin-treated mice, a model of type 1 diabetes. Patch-clamp recordings from DMV neurons in vitro revealed that FGF19 application altered synaptic and intrinsic membrane properties of DMV neurons, with the balance of FGF19 effects being significantly modified by a recent history of systemic hyperglycemia. These findings identify central parasympathetic circuitry as a novel target for FGF19 and suggest that FGF19 acting in the dorsal hindbrain can alter vagal output to produce its beneficial metabolic effects.
成纤维细胞生长因子 19（FGF19）是一种蛋白激素，当在大脑前脑室内给药时会产生抗糖尿病作用。然而，尚无研究探讨 FGF19 如何影响直接参与系统葡萄糖调节自主控制的后脑神经元。在背侧后脑中，迷走神经背核（DMV）的副交感运动神经元表达成纤维细胞生长因子受体，其活性调节内脏稳态过程，包括能量平衡。本研究检验了 FGF19 在脑内作用以改变 DMV 神经元兴奋性并降低血糖浓度的假设。第四脑室给予 FGF19 对对照小鼠的血糖浓度没有影响，但在链脲佐菌素处理的小鼠中，即 1 型糖尿病模型中，可诱导长达 12 小时的显著、外周毒蕈碱受体依赖性的全身高血糖降低。体外 DMV 神经元的膜片钳记录显示，FGF19 应用改变了 DMV 神经元的突触和内在膜特性，而 FGF19 作用的平衡受到近期全身高血糖的显著影响。这些发现确定了中枢副交感神经回路是 FGF19 的一个新靶点，并表明 FGF19 在背侧后脑中的作用可以改变迷走神经输出以产生其有益的代谢作用。
