A study to determine the contribution of renal glucose production to total glucose output in patients with insulin-secreting tumors. The hypoglycemia associated with insulin-secreting tumors is due, in part, to supression of hepatic glucose output (HGO)(1,2). During a fast, blood sugar levels are maintained by a reduction in plasma insulin and an increase in the production of glucose by the liver. It is thought that the kidney contributes a small fraction of the glucose production. The extent of its production is not yet known. Recent studies have suggested that insulin regulates both liver and kidney glucose production when given intravenously. But in patients with an insulin-secreting tumor (insulinoma), a large portion of the insulin released is taken up by the liver, and the kidney is exposed to a considerably smaller amount of insulin. Thus, it is likely that during a fast, the contribution of the kidney to overall glucose production increases to a greater extent in insulinoma patients compared to those without a tumor. Study subjects will be admitted to the Clinical Research Center for a three-day-fast where nothing but ice chips and water will be consumed for 72 hours. Percentage of body fat will be measured by placing EKG (electrocardiogram) electrodes on the hands and feet (bioimpedence) of the subjects and by measuring the thickness of skinfolds. Metabolic rate will also be determined. Oxygen intake and carbondioxide output will be measured by placing a loosely fitting plastic tent over the head of the quietly lying patient (indirect calorimetry). A urine sample will be obtained to determine the amount of protein the body is using for energy. Two intravenous catheters will be inserted, one to infuse non-radioactive tracers to determine the amount of glucose the liver is making, and the other to obtain blood samples. After a baseline period when a salt solution is infused along with the non-radioactive glucose, a second infusion containing radioactive amino acids will be infused for three hours. Blood samples will be drawn before and after the infusion to measure the amount of glucose made by the liver and the amount of alanine (white crystaline amino acids) that is converted to glucose, and indirect calorimetry will be repeated. At the conclusion of the infusion studies, the fast will continue and new blood samples will show amounts of glucose and insulin. After 72 hours or when the blood sugar level falls below 40mg./dl, an intravenous infusion of glucagon will be given to help raise the blood sugar. Blood samples will be obtained every 15 minutes for the next hour and then the subject will be fed. If an insulin-secreting tumor is present, the patient may receive surgical removal at MCV Hospitals. A small liver biopsy will determine the amount of certain enzymes which are involved in liver production. After 6 months, another visit to the CRC will determine if there is increased liver glucose production by overnight infusion studies.
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