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Optogenetic stimulation of vagal nerves for enhanced glucose-stimulated insulin secretion and β cell proliferation

Yohei Kawana1, Junta Imai2, Yosuke M Morizawa3

  • 1Department of Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan.

Nature Biomedical Engineering
|November 9, 2023
PubMed

Insights

Optogenetic stimulation of the vagal nerve enhances insulin secretion and pancreatic beta cell proliferation. These novel methods offer potential new therapies for diabetes by precisely controlling nerve signals.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Biomedical Engineering

Background:

  • Diabetes mellitus is a metabolic disorder characterized by impaired insulin secretion and beta cell function.
  • The vagal nerve plays a crucial role in regulating insulin secretion and beta cell proliferation, but effective stimulation methods are lacking.
  • Optogenetics offers precise control over neural activity, presenting a potential solution for targeted vagal nerve stimulation.

Purpose of the Study:

  • To develop and evaluate optogenetic techniques for selective and prolonged vagal nerve stimulation.
  • To investigate the impact of vagal nerve stimulation on glucose-stimulated insulin secretion and pancreatic beta cell proliferation.
  • To assess the therapeutic potential of these optogenetic methods in a mouse model of diabetes.

Main Methods:

  • Developed two optogenetic strategies for vagal nerve stimulation in mice expressing channelrhodopsin-2.
  • Method 1: Subdiaphragmatic implantation of an optical fiber for blue-light photostimulation of cholinergic neurons.
  • Method 2: Intra-pancreatic duct delivery of lanthanide microparticles for near-infrared activation of vagal fibers.

Main Results:

  • Both optogenetic methods successfully enhanced glucose-stimulated insulin secretion.
  • Optogenetic stimulation promoted pancreatic beta cell proliferation.
  • The second method, utilizing near-infrared light, suppressed streptozotocin-induced hyperglycemia in mice.
  • Demonstrated that vagal nerve signals, particularly those innervating the pancreas, are sufficient to regulate insulin secretion and beta cell growth.

Conclusions:

  • Optogenetic stimulation of the vagal nerve is a viable strategy for enhancing insulin secretion and beta cell proliferation.
  • These findings highlight the therapeutic potential of vagal nerve modulation for diabetes treatment.
  • The developed optogenetic tools provide precise control for future research into neuro-endocrine regulation.

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