The Effect of Glucagon on Net Splanchnic Balances of Glucose, Amino Acid Nitrogen, Urea, Ketones, and Oxygen in Man*

799

378

Section: Resultssupporting

confidence: 92%

“…Estimations of net splanchnic glucose production in man after an overnight fast vary from 122 to 420 g/day (3)(4)(5)(6)(7), an amount which corresponds to approximately one-half of the basal caloric turnover. Were glucose production from amino acids to continue at this rate, all body protein would be consumed within several weeks.…”

Section: Introductionmentioning

confidence: 99%

Liver and kidney metabolism during prolonged starvation

Owen¹,

Felig²,

Morgan³

et al. 1969

799

378

“…In particular a decreased splanchnic or liver blood flow could result in less insulin release into the general circulation without any change in pancreatic response. Studies of hepatic blood flow in man with doses of epinephrine comparable to those used in our study have shown, however, that increased rather than decreased splanchnic blood flow would be expected (19,20). We have estimated splanchnic blood flow with indocyanine green (21,22) in two subjects by using a central injection site and peripheral blood sampling site (23).…”

Section: Discussionmentioning

confidence: 84%

The effect of epinephrine on immunoreactive insulin levels in man.

Porte¹,

Graber²,

Kuzuya³

et al. 1966

506

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

“…The splanchnic metabolic alterations seen in the current study are particularly favorable for splanchnic glucose production and emphasize the important role of the splanchnic bed, as the major store of glycogen and the major site of gluconeogenesis (54), in regulation of circulating glucose levels. Metabolic changes after infectious injury have long been attributed to changes in circulating counterregulatory hormones (4)(5)(6)(7)(8)(9)32). After the current endotoxin challenge, the only counterregulatory hormone demonstrating a persistent change in circulating level was cortisol.…”

Section: Methodsmentioning

confidence: 99%

“…The roles of classical hormones such as the catecholamines, cortisol, and glucagon have been studied (3,4). Persistent elevations of combinations ofglucagon, epinephrine, or cortisol produced by constant infusions of these hormones mimic some of the changes seen in injury (5)(6)(7)(8)(9)(10). However, the correlation between alterations in circulating levels of such hormones and the metabolic changes acutely induced by infection is still poorly characterized.…”

Section: Introductionmentioning

confidence: 99%

The acute splanchnic and peripheral tissue metabolic response to endotoxin in humans.

Fong

Marano²,

Moldawer³

et al. 1990

349

151

The in vivo alterations in organ-specific substrate processing and endogenous mediator production induced by endotoxin were investigated in healthy volunteers. An endotoxin bolus (20 U/kg) produced increased energy expenditure, hyperglycemia, hypoaminoacidemia, and an increase in circulating free fatty acids. These changes included increased peripheral lactate and free fatty acid output, along with increased peripheral uptake of glucose. Coordinately, there were increased splanchnic uptake of oxygen, lactate, amino acids, and free fatty acids, and increased splanchnic glucose output. There were no changes in circulating glucagon, or insulin and transient changes in epinephrine and cortisol were insufficient to explain the metabolic changes. Plasma cachectin levels peaked 90 min after the endotoxin infusion, and hepatic venous (HV) cachectin levels (peak 250±50 pg/ml) were consistently higher than arterial levels (peak 130±30 pg/ml, P < 0.05 vs. HV). No interleukin la or 1,8 was detected in the circulation. Circulating interleukin 6, measured by B.9 hybridoma proliferation, peaked 2 h after the endotoxin challenge (arterial, 16±2 U/ml; HV, 21±3 U/ml). The net cachectin efflux (-7 Mg) from the splanchnic organs demonstrates that these tissues are a major site for production of this cytokine. Hence, splanchnic tissues are likely influenced in a paracrine fashion by regional cachectin production and may also serve as a significant source for systemic appearance of this cytokine.