Optogenetic stimulation of cholinergic fibers for the modulation of insulin and glycemia

Sci Rep. 2021 Feb 11;11(1):3670. doi: 10.1038/s41598-021-83361-3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / metabolism
  • Blood Glucose / genetics
  • Channelrhodopsins / genetics
  • Choline O-Acetyltransferase / genetics
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / pathology
  • Cholinergic Neurons / metabolism
  • Cholinergic Neurons / pathology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Disease Models, Animal
  • Glucagon / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / biosynthesis
  • Insulin / metabolism*
  • Insulin / radiation effects
  • Insulin Secretion / genetics
  • Insulin Secretion / radiation effects
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / radiation effects
  • Mice
  • Optogenetics / trends
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Vagus Nerve / metabolism*
  • Vagus Nerve / pathology
  • Vagus Nerve Stimulation


  • Blood Glucose
  • Channelrhodopsins
  • Insulin
  • Glucagon
  • Choline O-Acetyltransferase
  • Glucose