Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21224, USA.
Transtimulation Research, Inc, Oklahoma City, OK, USA.
Obes Surg. 2019 Sep;29(9):2869-2877. doi: 10.1007/s11695-019-03901-9.
Vagal nerve stimulation (VNS) has been reported to reduce body weight and improve sympathovagal imbalance in both basic and clinical studies. Its effects on glycemic control were however unclear. The aims of this study were to investigate the effects of VNS with various parameters on blood glucose and its possible mechanisms in rats.
A hyperglycemic rodent model induced by glucagon was used initially to optimize the VNS parameters; then, a type 2 diabetic rodent model induced by high-fat diet combined with streptozotocin was used to validate the VNS method. The VNS electrodes were implanted at the dorsal subdiaphragmatic vagus; three subcutaneous electrodes were implanted at the chest area for recording electrocardiogram in rats induced by glucagon.
(1) VNS with short pulse width of 0.3 ms but not 3 ms reduced blood glucose during an oral glucose tolerance test (OGTT), with a 38.4% reduction at 15 min and 26.9% at 30 min (P < 0.05, vs. sham-VNS respectively). (2) VNS at low frequency of 5 Hz but not 14 Hz or 40 Hz reduced blood glucose during the OGTT (P < 0.05, vs. sham-VNS). (3) Intermittent VNS was more potent than continuous VNS (P < 0.01). (4) No difference was found between unilateral VNS and bilateral VNS. (5) VNS enhanced vagal activity (P = 0.005). (6) The hypoglycemic effect of VNS was blocked by glucagon-like peptide-1 (GLP-1) antagonist exendin-4.
VNS at 5 Hz reduces blood glucose in diabetic rats by enhancing vagal efferent activity and the release of GLP-1.
迷走神经刺激（VNS）已在基础和临床研究中被报道可减轻体重并改善交感神经迷走神经失衡。然而，其对血糖控制的影响尚不清楚。本研究旨在探讨不同参数的 VNS 对血糖的影响及其在大鼠中的可能机制。
首先使用胰高血糖素诱导的高血糖啮齿动物模型来优化 VNS 参数；然后，使用高脂肪饮食联合链脲佐菌素诱导的 2 型糖尿病啮齿动物模型来验证 VNS 方法。VNS 电极植入膈下游离神经背侧；在接受胰高血糖素诱导的大鼠胸部区域植入三个皮下电极以记录心电图。
（1）脉宽为 0.3ms 的短脉冲 VNS 而非 3ms 的 VNS 在口服葡萄糖耐量试验（OGTT）期间降低血糖，15 分钟时降低 38.4%，30 分钟时降低 26.9%（P<0.05，分别与 sham-VNS 相比）。（2）频率为 5Hz 的 VNS 而非 14Hz 或 40Hz 的 VNS 在 OGTT 期间降低血糖（P<0.05，与 sham-VNS 相比）。（3）间断 VNS 比连续 VNS 更有效（P<0.01）。（4）单侧 VNS 和双侧 VNS 之间没有差异。（5）VNS 增强了迷走神经活动（P=0.005）。（6）VNS 的降血糖作用被胰高血糖素样肽-1（GLP-1）拮抗剂 exendin-4 阻断。
5Hz 的 VNS 通过增强迷走神经传出活动和 GLP-1 的释放来降低糖尿病大鼠的血糖。
