Cervical vagal nerve stimulation impairs glucose tolerance and suppresses insulin release in conscious rats
Cervical vagal nerve stimulation impairs glucose tolerance and suppresses insulin release in conscious rats
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DOI：
10.14814/phy2.13953
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发表时间：
2018-12-01
影响因子：
2.5
通讯作者：
Lira, Vitor A.
中科院分区：
文献类型：
--
作者：
Stauss, Harald M.;Stangl, Hubert;Lira, Vitor A.
先前，我们报道了颈迷走神经刺激（VNS）通过传入信号提高麻醉大鼠的血糖水平并抑制胰岛素分泌。由于传入信号也被认为介导了VNS对难治性癫痫和重度抑郁症患者的治疗效果，那么用VNS治疗的患者是否会出现糖耐量受损的问题就出现了。因此，我们假设颈VNS损害清醒大鼠的葡萄糖耐量。大鼠（n = 7）使用遥测血压传感器和右侧或左侧颈迷走神经刺激器（3 V. 5 Hz， 1 msec脉冲持续时间，1 h开1 h关）。葡萄糖耐量试验（gtt， 1.5 g葡萄糖/kg BW， i.p.）在刺激器打开或关闭（假刺激）的情况下禁食一夜（随机顺序，间隔3-4天）。夜间VNS没有改变平均血压或心率水平，但增加了空腹血糖水平（140 +/- 13 mg/dL vs 109 +/- 8 mg/dL, P < 0.05）。VNS期间大鼠gtt血糖浓度曲线下面积明显大于假刺激（3499 +/- 211 mg/dL*h vs. 1810 +/- 234 mg/dL*h, P < 0.05）。与空腹基线水平相比，空腹1小时时血清胰岛素浓度下降（-0.57 +/- 0.25 ng/mL, P < 0.05），假性刺激时升高（+0.71 +/- 0.15 ng/mL, P < 0.05）。这些结果表明，慢性颈椎VNS可能通过抑制清醒大鼠葡萄糖诱导的胰岛素释放来提高空腹血糖水平并损害葡萄糖耐量。使用VNS治疗的患者是否有更高的发生葡萄糖耐受不良和2型糖尿病的风险仍有待确定。
Previously, we reported that cervical vagal nerve stimulation (VNS) increases blood glucose levels and inhibits insulin secretion in anesthetized rats through afferent signaling. Since afferent signaling is also thought to mediate the therapeutic effects of VNS in patients with therapy-refractory epilepsy and major depression, the question arises if patients treated with VNS develop impaired glucose tolerance. Thus, we hypothesized that cervical VNS impairs glucose tolerance in conscious rats. Rats (n = 7) were instrumented with telemetric blood pressure sensors and right- or left-sided cervical vagal nerve stimulators (3 V. 5 Hz, 1 msec pulse duration, 1 h on 1 h off). Glucose tolerance tests (GTTs, 1.5 g dextrose/kg BW, i.p.) were performed after overnight fasting with the stimulators on or off (sham stimulation) in randomized order separated by 3-4 days. Overnight VNS did not alter mean levels of blood pressure or heart rate, but increased fasted blood glucose levels (140 +/- 13 mg/dL vs. 109 +/- 8 mg/dL, P < 0.05). The area under the blood glucose concentration curves of the GTTs was larger during VNS than sham stimulation (3499 +/- 211 mg/dL*h vs. 1810 +/- 234 mg/dL*h, P < 0.05). One hour into the GTTs, the serum insulin concentrations had decreased during VNS (-0.57 +/- 0.25 ng/mL, P < 0.05) and increased during sham stimulation (+0.71 +/- 0.15 ng/mL, P < 0.05) compared to the fasted baseline levels. These results demonstrate that chronic cervical VNS elevates fasted blood glucose levels and impairs glucose tolerance likely through inhibition of glucose - induced insulin release in conscious rats. It remains to be determined if patients treated with VNS are at greater risk of developing glucose intolerance and type 2 diabetes.