Innovative and Innervating Ways to Monitor Blood Glucose

Innovative and Innervating Ways to Monitor Blood Glucose

By Alex Parrott

Manipulating the nervous system through stimulation has already proven to have a wide range of applications. More specifically, the vagus nerve and peripheral nerves around the pancreas, if manipulated correctly, can have very interesting results for controlling blood glucose levels. Both Dr. Sarah Stanley and Dr. Yin’s research teams have found ways to stimulate insulin release from the body by stimulating these nerves.

Dr. Stanley’s team innervated the nerves around the pancreas in diabetic transgenic mice models, since the pancreas already needs heavy neural activity to modify glucose levels. Past studies have looked at stimulating the vagus and splanchnic nerves but ran into issues with stimulating other nerves leading to off-target intra-abdominal organs. How did they get around this? New scientific advances in neuromodulation tools have allowed for temporary control of specific organ innervation to study their specific roles. This approach led Dr. Stanley’s team to develop a way to wirelessly regulate certain areas so as to understand how their pathways played a role in pancreatic functions. They used non-viral and viral tracers to map out the nervous system, and then tethered TRPV1 to ferritin, an iron protein. The TRPV1-ferritin was introduced through a neural pathway and then stimulated with a magnetic field, resulting in the release of intracellular calcium and depolarization in vitro and ex vivo. Could this lead to insulin release from beta cells?

While Dr. Stanley’s team used a magnetic field to promote insulin release, Dr. Yin’s team applied results from V-BLOC and high frequency stimulation to activate the vagus nerve using a pulse generator in a hyperglycemic canine model. Dr. Yin used a low frequency pulse generator to therapeutically stimulate the vagus nerve through leads placed along the ventral trunk, resulting in the release of GLP-1, which has been proven to promote insulin secretion and expansion of insulin secreting beta cell mass. Through multiple tests and experiments with different frequencies and durations, Dr. Yin’s team  was able to reduce glucose levels from 15.3 to 32.2 percent. Dr. Yin’s abstract stated, “Intermittent vagal nerve stimulation (VNS) at a frequency of 5 or 10 Hz was found to be the best stimulation parameters. This VNS method at the dorsal trunk for 180 min reduced blood glucose from 171±12.1mg/dl with sham VNS to 140.4±10.6mg/dl with VNS at 30min and from 156.6±12.0mg/ml to 111.8±12.5mg/dl at 90min.” 

But what does this mean?

Both of these studies lead to promising ways of regulating diabetic glucose levels without having to depend as much on traditional insulin delivery methods. If beta cells can release insulin through neuromodulation then this would be a major breakthrough and alternative to having to use an external insulin pump. If this research is continually pursued and refined, it could lead to many benefits, including cheaper diabetes treatment costs and fewer risk factors for diabetics.

Sources 

  • Pérez C, Stanley S, Wysocki RW, Havranova J, Ahrens-Nicklas R, Onyimba F, Friedman JM. Molecular annotation of integrative feeding neural circuits. Cell Metab. 2011 Feb 2;13(2):222-32.
  • Stanley S, Gagner JE, Damanpour S, Yoshida S, Dordick JS, Friedman JM. Radio-Wave Heating of Iron Oxide Nanoparticles Can Regulate Plasma Glucose in Mice. Science, 2012 May 4 2012, VOL 336, 604-607
  • Stanley S, Domingos AI, Kelly L, Garfield A, Damanpour S, Heisler L, Friedman JM. Profiling of Glucose-sensing Neurons reveals that GHRH Neurons are activated by Hypoglycemia. Cell Metabolism, 2013, Oct 1, 18(4), 596-607
  • Camilleri M, Toouli J, Herrera MF, Kulseng B, Kow L, Pantoja JP, Marvik R, Johnsen G, Billington CJ, Moody FG, Knudson MB, Tweden KS, Vollmer M, Wilson RR, Anvari M. Intra-abdominal vagal blocking (VBLOC therapy): clinical results with a new implantable medical device. Surgery. 2008 Jun;143(6):723-31. doi: 10.1016/j.surg.2008.03.015. Epub 2008 May 9. PMID: 18549888.
  • MacDonald, Patrick E., et al. “The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion.” Diabetes, American Diabetes Association, 1 Dec. 2002, diabetes.diabetesjournals.org/content/51/suppl_3/S434.

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