Amplitude modulation of pulsatile insulin secretion by intrapancreatic ganglion neurons.
Amplitude modulation of pulsatile insulin secretion by intrapancreatic ganglion neurons.
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DOI：
10.2337/diabetes.50.1.51
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发表时间：
2001
期刊：
影响因子：
7.7
通讯作者：
Lei Sha;J. Westerlund;J. Szurszewski;Peter Bergsten
中科院分区：
文献类型：
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作者：
Lei Sha;J. Westerlund;J. Szurszewski;Peter Bergsten
同时测量 33 个胰腺内犬神经节和神经节附近胰腺实质的神经元活性和胰岛素释放。用细胞内微电极记录神经节单个神经元的电活动，并用酶联免疫吸附测定测定附着胰岛的胰岛素释放。在存在 10 mmol/l 葡萄糖和脉动（3.7 +/- 0.4 分钟/脉冲）的情况下，胰岛素释放为 62 +/- 18 fmol 制剂/分钟。神经元电活动的相应测量显示稳定的膜电位为-53.5 +/- 0.6 mV。短时高频 (20 Hz) 节前神经刺激可诱发动作电位，并且在 46% 的制剂中，与胰岛素脉冲幅度增加相关的胰岛素分泌率增加三倍。 10 微摩尔/升河豚毒素 (TTX) 可阻断该作用。在其他制剂中，连续低频（0.05-0.5 Hz）节前神经刺激诱发动作电位，并且在 50% 的制剂中，胰岛素释放逐渐增加，与胰岛素脉冲幅度的增加相关，而不改变持续时间。 50 微摩尔/升六甲铵 (HEX) 可阻断该作用。在其余的制剂中，在神经刺激期间没有观察到胰岛素释放的变化。在没有刺激的情况下，TTX 和 HEX 都不影响膜电位或胰岛素分泌。这些对胰内神经节活动和胰岛素分泌的首次同时测量与胰内神经节神经元群体电活动变化引起的脉动胰岛素分泌的幅度调节一致。
Neuron activity and insulin release were measured simultaneously from 33 preparations of intrapancreatic canine ganglia and pancreatic parenchyma adjacent to the ganglia. The electrical activity of single neurons of the ganglia was recorded with intracellular microelectrodes, and insulin release from the attached islets was determined with an enzyme-linked immunosorbent assay. Insulin release was 62 +/- 18 fmol preparation/min in the presence of 10 mmol/l glucose and pulsatile (3.7 +/- 0.4 min/pulse). Corresponding measurements of neuronal electrical activity showed a stable membrane potential of -53.5 +/- 0.6 mV. Short, high-frequency (20 Hz) preganglionic nerve stimulation evoked action potentials and, in 46% of the preparations, a threefold rise in the insulin secretory rate associated with increased amplitude of the insulin pulses. The effects were blocked by 10 micromol/l tetrodotoxin (TTX). In other preparations, continuous low-frequency (0.05-0.5 Hz) preganglionic nerve stimulation evoked action potentials and, in 50% of the preparations, a gradual increase of insulin release associated with augmentation of insulin pulse amplitude without alteration of the duration. The effects were blocked by 50 micromol/l hexamethonium (HEX). In the remaining preparations, no change in insulin release was observed during nerve stimulation. In the absence of stimulation, neither TTX nor HEX affected the membrane potential or insulin secretion. These first simultaneous measurements of intrapancreatic ganglion activity and insulin secretion are consistent with amplitude modulation of pulsatile insulin secretion induced by changes in electrical activity in a population of intrapancreatic ganglion neurons.