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Publication : Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia.

First Author  Fontaine AK Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  3670
PubMed ID  33574598 Mgi Jnum  J:303750
Mgi Id  MGI:6512769 Doi  10.1038/s41598-021-83361-3
Citation  Fontaine AK, et al. (2021) Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia. Sci Rep 11(1):3670
abstractText  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.
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