This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A study to determine the role of the presence of an excess amount of insulin in the blood arising from causes within the body (endogenous hyperinsulinemia) on the formation of glucose from molecules in the kidneys that are not carbohydrates (renal gluconeogenesis). It is well known that hypoglycemia (low blood sugar) associated with insulin-secreting pancreatic tumors is due, in part, to suppression of hepatic glucose output (HGO). Recent studies have suggested that insulin regulates both liver and kidney glucose production when given intravenously. In patients with an insulin-secreting tumor (insulinoma) a large portion of the insulin released is taken up by the liver and the kidneys are exposed to a considerably smaller amount of insulin. Thus, it is likely that the contribution of the kidneys to overall glucose production increases to a greater extent in insulinoma patients compared to patients without a tumor during a fast. 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 kidneys produce a small fraction of the glucose produced. However, the extent is unknown. This study is designed to examine the potential role of the kidney in glucose production. Study subjects will be admitted to the General Clinical Research Center for a three day fast. Blood samples will be obtained periodically by a fingerstick in order to monitor blood sugar. More blood samples will be obtained from a catheter. Glucagon will be administered if blood glucose values fall to below 40 mg/dl or the subject develops hypoglycemic symptoms. If the subject has an insulin-secreting tumor, another short study will begin. If there is no tumor, subjects will be asked to participate in the same studies on the third day of the fast. Subjects will be given """"""""heavy water"""""""", a natural variant of water which is non-radioactive. Later, two catheters will be placed into arm veins, one to infuse non-radioactive tracers to determine the amount of glucose the liver is making and one to obtain blood samples. Oxygen use, carbon dioxide production, and protein in the urine will be measured. An amino acid infusion will be given after blood samples are taken. In patients with a tumor, lipids and heparin will be given. A final infusion of glucagon will be given and blood samples will be taken.
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