Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia.
Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia.
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DOI：
10.1038/s41598-021-83361-3
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发表时间：
2021-02-11
影响因子：
4.6
通讯作者：
Benninger RKP
中科院分区：
文献类型：
--
作者：
Fontaine AK;Ramirez DG;Littich SF;Piscopio RA;Kravets V;Schleicher WE;Mizoguchi N;Caldwell JH;Weir RFF;Benninger RKP
先前的研究已经证明迷走神经电刺激刺激内分泌胰腺功能。虽然这会增加胰岛素分泌，但不会发生预期的循环葡萄糖伴随降低。一个复杂的因素是电神经刺激的非特异性。然而，光遗传学工具提供了使用遗传靶向和/或空间成形的激发光进行细胞类型特异性神经刺激的潜力。在这里，我们展示了光激活刺激内分泌胰腺靶向副交感神经（胆碱能）轴突。在胆碱能细胞中表达ChR 1视紫红质2（ChR 2）的小鼠模型中，响应于（1）胰腺中轴突末端的超声图像引导光学刺激或（2）颈部迷走神经轴突的光学刺激，测量血清胰岛素和葡萄糖。在基础葡萄糖和葡萄糖刺激条件下进行测量。在胰腺和颈部迷走神经刺激下，相对于对照组，血浆胰岛素显着增加，而在胰腺刺激下观察到血糖水平迅速降低。此外，在胰腺刺激下，胰腺中基于超声的血流测量值增加。总之，这些结果证明了体内光遗传学用于研究内分泌胰腺功能的神经调节的实用性，并表明其用于控制胰岛素分泌和葡萄糖稳态的治疗潜力。
Previous studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion, expected concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools, however, provide the potential for cell-type specific neural stimulation using genetic targeting and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine pancreas by targeting parasympathetic (cholinergic) axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to (1) ultrasound image-guided optical stimulation of axon terminals in the pancreas or (2) optical stimulation of axons of the cervical vagus nerve. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and cervical vagal stimulation, while a rapid reduction in glycemic levels were observed under pancreatic stimulation. Additionally, ultrasound-based measurements of blood flow in the pancreas were increased under pancreatic stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest its therapeutic potential for the control of insulin secretion and glucose homeostasis.