The mechanisms by which epinephrine elevates the blood sugar have been of considerable interest for more than 25 years. In an extensive review in 1956, Ellis suggested that the two major influences on glucose metabolism were increased glycogenolysis in the liver and peripheral tissues, and direct inhibition of glucose uptake by muscle (1). There is, however, the additional possibility that epinephrine might decrease insulin levels. The introduction of insulin immunoassay (2, 3) has allowed us to examine this third hypothesis in man. Our data show that epinephrine infusion is not associated with a rise in serum immunoreactive insulin (IRI) despite significant hyperglycemia. In addition, epinephrine was found to inhibit the expected rise in IRI after administration of exogenous glucose, glucagon, and tolbutamide. medical illness. None had any close relative who was known to be diabetic. All were within 15% of their ideal body weight.' Approximately 20% had been previously tested at random with the 100-g oral glucose tolerance test and were normal by the criteria of Mosenthal and Barry (4). All had fasting plasma glucose less than 105 mg per 100 ml. For the study, no solid food was taken after the previous evening meal at 6 to 7 p.m., and no liquids except water were taken after midnight.
MethodsNo smoking was allowed on the day of the test. Upon arriving at the Clinical Research Center for study the volunteer was put to bed, and a slow intravenous 0.85%oNaCl drip was begun through each of two indwelling venous plastic catheters. Blood samples were taken through one catheter, and drugs or glucose was infused through the other with a constant drive syringe infusion pump. No anticoagulants were given to the patient or were present in the sampling syringe. Blood samples were obtained every 15 minutes and sampled for measurements of glucose, IRI, free fatty acids (FFA), and glycerol. Blood for insulin assay was allowed to clot for I hour at room temperature, and the serum was frozen at -190 C until analyzed by the double antibody immunoprecipitation technique (5). Neither epinephrine (1 ,ug per ml) nor tolbutamide (50 mg per ml) had any measurable effects when added to the immunoassay system in vitro. The glucagon preparation assayed 5 to 7 AsU of immunoreactive insulin per microgram of glucagon. This amount of insulin was considered to have no significant effect upon serum IRI with the infusion rate of glucagon used (5 sAg per minute). The human insulin standard was supplied.2 Blood samples for FFA, glucose, and glycerol were anticoagulated with heparin and kept chilled at 40 C. The plasma was separated by centrifugation in the cold and frozen at -19°C for future analysis. FFA were titrated against standard base by a modified Dole procedure (6). Plasma glucose was measured by a Technicon autoanalyzer with a ferricyanide reagent. Glycerol was measured by the enzymatic method of Wieland (7) with commercially available glycerokinase and glycerophosphate dehydrogenase.8