1533-P: Mind over Metabolism—A Molecular Subtype of Vagal Neurons That Can Improve Glucose Tolerance

Abstract

Parasympathetic neurons of the dorsal motor nucleus of the vagus (DMV) control glucose metabolism through the vagus nerve and so are potential targets for diabetes treatment. Currently, little is known about the molecular identity or organization of the glucose-regulating DMV neurons. To identify these neurons for further study, we optogenetically activated them in awake mice during a glucose tolerance test (GTT). We transgenically targeted a blue light-sensitive ion channel, CaTCh, selectively to all DMV neurons based on co-expression of Chat - and Phox2b- driven recombinases (Chat-Cre::Phox2b-Flp::CaTCh mice). We implanted optical fibers over the DMV in these adult mice (2 females, 1 male), acclimated them to the test environment and procedure, and then fasted them overnight. After recording baseline glucose levels, we administered intraperitoneal glucose (20% glucose, 10uL/g) and concurrently began photostimulation (time=0-30min; 5Hz, 1ms pulse, 2.5s off, 1s on) or sham stimulation. We performed tail blood glucometry at 5-min increments from -20-120min and compared average readings between stimulation and sham trials. Results: sham 0-30min 472.6 ± 74mg/dL, stim 0-30min 352 ± 48mg/dL (p=0.0005, paired t-test); other timepoints, p>0.05 between conditions. Our results indicate that activating DMV neurons can significantly improve glucose tolerance. To identify specific DMV neurons controlling glucose tolerance, we optogenetically activated a molecular subtype of DMV neurons defined by co-expression of Calb2 and Chat (2 female Calb2-Cre::Chat-Flp::CaTCh adult mice). We photostimulated Calb2+ DMV neurons while performing GTT as described above. Results: sham 0-30min 493 ± 90mg/dL, stim 0-30min 407 ± 69mg/dL (p=0.0390, paired t-test); other timepoints, p>0.05 between conditions. Together our data indicates that activating DMV neurons generally or Calb2+ DMV neurons specifically improves glucose tolerance. Disclosure N.J.Conley: None. L.S.Kauffman: None. J.Campbell: None. Funding American Diabetes Association (1-18-INI-14 to J.C.)