Vagal Nerve Stimulation and Glucose Metabolism

The overall aim of this application is to determine the mechanism(s) by which common
bariatric surgical procedures alter carbohydrate metabolism. Very often, resolution of
diabetes occurs in the early post-operative period prior to the development of significant
weight loss. It has been suggested that bariatric surgery alters insulin action but few
studies have examined insulin secretion or postprandial glucose fluxes in such patients. At
the present time, little is known about how the various bariatric surgical procedures alter
glucose homeostasis. It is essential that the effect of bariatric surgery and meal size on
these parameters be understood and accurately measured. Enteroendocrine secretion is
affected by the rate of intestinal delivery of calories and may also be modulated by the
enteric nervous system and the rate of direct delivery of nutrients to enteroendocrine
cells. Direct measurement of intestinal transit is also an important part of understanding
how bariatric surgery alters intestinal secretion of hormones that may alter glucose
metabolism. The Oral and C-peptide Minimal Models when applied to C-peptide, glucose and
insulin concentrations after ingestion of a standard labeled mixed meal can accurately
measure insulin secretion and action. Subsequently, the disposition index provides a
measurement of the appropriateness of insulin secretion for the prevailing insulin action.
When coupled with established triple-tracer methodology, a mixed meal can be used to measure
fasting and postprandial glucose fluxes. Though the vagal trunks are preserved during
bariatric surgery, gastric transection during the formation of a gastric pouch for RYGB, or
during the sleeve gastrectomy for the duodenal switch procedure, may denervate post-gastric
organs including the pancreas and intestine. Reversible vagal block results in weight loss,
decreased caloric intake, earlier satiation and reduced hunger. The effect of this form of
vagal denervation on glycemic control is unclear. There is evidence that hepatic
parasympathetic input regulates insulin action in rodents. Vagal afferents are also
important in hepatoportal glucose sensing.