Vagal Nerve Stimulation and Glucose Metabolism

• Disposition Index [ Time Frame: Compared to VNS on or off ] [ Designated as safety issue: No ]
  The appropriateness of insulin secretion for the prevailing degree of insulin action is assessed by calculating the total disposition index (DItotal), which equals the product of insulin secretion and insulin sensitivity.
  
  

• Gastric Emptying [ Time Frame: Compared to VNS on or off ] [ Designated as safety issue: No ]
  Gastric emtpying will be measured by anterior and posterior gamma camera images obtained immediately after meal ingestion, every 15 minutes for the first 2 hours, then every 30 minutes for the next 2 hours (total 4 hours after the meal) for gastric emptying measurements
  
  

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.