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Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons

Arjun K. Fontaine, David G. Ramirez, Samuel F. Littich, Robert A. Piscopio, Vira Kravets, John H. Caldwell, Richard F. Weir, Richard K.P. Benninger
doi: https://doi.org/10.1101/2019.12.21.885970
Arjun K. Fontaine
1Department of Bioengineering, University of Colorado – Anschutz Medical Campus
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  • For correspondence: arjun.fontaine@ucdenver.edu
David G. Ramirez
1Department of Bioengineering, University of Colorado – Anschutz Medical Campus
3Barbara Davis Center for Childhood Diabetes – Anschutz Medical Campus
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Samuel F. Littich
1Department of Bioengineering, University of Colorado – Anschutz Medical Campus
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Robert A. Piscopio
3Barbara Davis Center for Childhood Diabetes – Anschutz Medical Campus
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Vira Kravets
3Barbara Davis Center for Childhood Diabetes – Anschutz Medical Campus
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John H. Caldwell
2Department of Cell and Developmental Biology, University of Colorado – Anschutz Medical Campus
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Richard F. Weir
1Department of Bioengineering, University of Colorado – Anschutz Medical Campus
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Richard K.P. Benninger
1Department of Bioengineering, University of Colorado – Anschutz Medical Campus
3Barbara Davis Center for Childhood Diabetes – Anschutz Medical Campus
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Abstract

Previous studies have demonstrated stimulation of endocrine pancreas function by vagal nerve electrical stimulation. While this increases insulin secretion; concomitant reductions in circulating glucose do not occur. A complicating factor is the non-specific nature of electrical nerve stimulation. Optogenetic tools enable high specificity in neural stimulation using cell-type specific targeting of opsins and/or spatially shaped excitation light. Here, we demonstrate light-activated stimulation of the endocrine pancreas by targeting vagal parasympathetic axons. In a mouse model expressing ChannelRhodopsin2 (ChR2) in cholinergic cells, serum insulin and glucose were measured in response to both ultrasound image-guided optical stimulation of axon terminals in the pancreas and optical stimulation of axons of the cervical vagus nerve, together with ultrasound-based measures of pancreas blood flow. Measurements were made in basal-glucose and glucose-stimulated conditions. Significant increases in plasma insulin occurred relative to controls under both pancreas and vagal stimulation, accompanying rapid reductions in glycemic levels. Additionally, a significant increase in pancreatic blood flow was measured following optical stimulation. Together, these results demonstrate the utility of in-vivo optogenetics for studying the neural regulation of endocrine pancreas function and suggest therapeutic potential for the control of insulin secretion and glucose homeostasis.

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Posted December 23, 2019.
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Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons
Arjun K. Fontaine, David G. Ramirez, Samuel F. Littich, Robert A. Piscopio, Vira Kravets, John H. Caldwell, Richard F. Weir, Richard K.P. Benninger
bioRxiv 2019.12.21.885970; doi: https://doi.org/10.1101/2019.12.21.885970
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Optogenetic Stimulation of Pancreatic Function via Vagal Cholinergic Axons
Arjun K. Fontaine, David G. Ramirez, Samuel F. Littich, Robert A. Piscopio, Vira Kravets, John H. Caldwell, Richard F. Weir, Richard K.P. Benninger
bioRxiv 2019.12.21.885970; doi: https://doi.org/10.1101/2019.12.21.885970

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