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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 307 records · Page 17Linked to original sources
PubMed1983

Ketone-glucose interaction in fed, fasted, and fasted-infected sheep.

Ketosis following starvation was suppressed by hindlimb infection in seven fasted sheep. Glucose production determined following the primed constant infusion of [6-3H(N)]glucose was elevated in the fasted-infected animals (9.50 +/- 1.11 mmol X kg-1 X min-1 (mean +/- SE) versus fasted controls (5.56 +/- 2.2). To determine if the ketonemia following sepsis contributed to the increased glucogenesis associated with catabolic disorder, glucose production and arterial substrates were measured before and after infusion of sodium-DL-beta-hydroxybutyrate (beta-OHB, 20 mumol X kg-1 X min-1) in fed, fasted, and fasted-infected animals. Following 3 h of beta-OHB infusion in the awake conditioned animals, beta-OHB and acetoacetate blood concentrations more than doubled. With infusion, blood glucose and alanine concentrations decreased in the fed and fasted sheep but not in the fasted-infected group. Glucose production fell significantly from 10.11 +/- 1.33 to 8.44 +/- 1.05 in the fed animals and from 5.05 +/- 0.28 to 4.11 +/- 0.33 in the fasted group. Glucose production was unaffected by beta-OHB infusion in the fasted-infected animals (9.50 +/- 1.83 vs. 9.11 +/- 1.44). The accelerated rate of glucose production in sheep following infection is not a consequence of the hypoketonemic state associated with sepsis.

Acidosis↗
PubMed1983

Thermic effect of infused glucose and insulin in man. Decreased response with increased insulin resistance in obesity and noninsulin-dependent diabetes mellitus.

The thermic effect of infused glucose and insulin was measured by combining the hyperinsulinemic euglycemic clamp technique with indirect calorimetry, in 10 normal weight volunteers (group I), 7 obese subjects with normal glucose tolerance (group II), and 13 obese subjects with abnormal glucose tolerance or noninsulin-dependent diabetes mellitus before (group IIIa) and after weight loss of 10.8 +/- 0.4 kg (group IIIb). During hyperinsulinemia (760-1,100 pmol/liter), total glucose disposal from combined endogenous production and glucose infusion was 545 +/- 49, 441 +/- 70, 233 +/- 35, 231 +/- 31 mg/min and energy expenditure changed by + 0.476 +/- 0.080, +0.293 +/- 0.095, -0.114 +/- 0.063, and +0.135 +/- 0.082 kJ/min in group I, II, IIIa, and IIIb, respectively. The increased energy expenditure correlated with glucose storage (measured cost of processing the glucose: 1.33 kJ/g). In group IIIa there was no increase in energy expenditure in response to glucose and insulin infusions. After therapy (group IIIb) there was a significant recovery (P less than 0.05) of the thermic effect of infused glucose although total glucose disposal was unchanged. It is proposed that the recovered thermic effect of infused insulin/glucose is due to the different contributions of gluconeogenesis in the fasting state and during the glucose clamp before and after weight loss. In addition we hypothesize that some of the lower thermic effect of food reported in obese noninsulin-dependent diabetics may be explained by decreased energy expenditure due to a greater suppression of hepatic gluconeogenesis as well as by lower storage rate.

Blood Glucose↗
PubMed1983

Energy metabolism in trauma and sepsis: the role of fat.

There seems little doubt that there are signals for the increased mobilization of fat in shock, trauma, and sepsis. Whether those signals are reflected by an actual increase in mobilization is dependent on many variables including cardiovascular status. A hypothetical scheme based on our own experiments in the hyperdynamics phases of response to burn injury and to sepsis is presented in Figure 8. According to this scheme, catecholamines stimulate lipolysis in the adipose tissue, resulting in the release of glycerol and FFA into the plasma at increased rates. The glycerol is cleared by the liver and converted into glucose--a process stimulated by, among other things, glucagon. Some of the increased flux of FFA is also cleared by the liver, whereupon the fatty acids are incorporated into VLDL and released again into the plasma. The increased FFA levels also exert a dampening effect on the factors stimulating hepatic glucose production. At the periphery, plasma FFA as well as VLDL fatty acids are taken up at an increased rate. The tissues are attuned to the oxidation of fat, and as a consequence most of the energy production is derived from fat oxidation. The increased fatty acids exert an inhibitory effect on the complete oxidation of glucose, so although glucose may be taken up at an accelerated rate, the relative contribution of glucose oxidation to total energy production may fall. Rather than being completely oxidized, pyruvate is reduced to lactate and released into the plasma at an accelerated rate. The lactate then contributes to the production of glucose in the liver, completing a cyclical process called the Cori Cycle. Although all aspects of this scheme are supported by data highlighted in this paper, it certainly must be an oversimplification of the overall response of substrate metabolism to trauma and sepsis. It is presented for the purpose of highlighting the potential role of fat as a controller of the metabolic response, and to suggest that the enhanced mobilization and oxidation of fat is one of the fundamental responses to stress.

Animals↗
PubMed1983

Isotopic approaches to the estimation of protein requirements in burn patients.

Determination of the protein requirement of the severely burned patient has been hampered by the lack of an appropriate means of evaluating the effects of various levels of intake. We have used two new isotopic techniques in an attempt to assess the effects of two levels of protein intake in six severely burned adult patients. A crossover experimental design enabled us to study each patient at the end of two 3-day dietary regimens. All diets were isocaloric and provided approximately 25% more calories than the measured energy expenditure (means = 40 Kcal/kg X day). In one regimen, each patient received 2.2 g protein/kg X day; during the other treatment period they received 1.4 g protein/kg X day. The patients were studied in the fed state and after 10-12 h of fasting. Leucine kinetics were determined by means of the primed-constant infusion of (1-13C)-leucine. We were able to distinguish the oxidation of plasma leucine from the oxidation of leucine derived from intracellular protein at the site of the deamination of leucine (predominantly muscle) by simultaneously determining both leucine and alpha-ketoisocaproic acid enrichment. Also, rates of whole-body protein synthesis and catabolism were calculated by means of another stable-isotope technique involving the infusion of (15N2)-urea. Finally, a third means of estimating net protein catabolism based on urinary N-excretion data was used at the same time that the isotopic studies were performed. The 13C-leucine data and the N-excretion data indicated that a balance between protein synthesis and catabolism could be achieved with a protein intake of 1.4 protein/kg X day. When protein intake was increased to 2.2 g protein/kg X day, neither isotopic method indicated a further beneficial effect on net protein synthesis, although the absolute rates of protein synthesis and catabolism were stimulated. The N-excretion data, however, indicated a significant improvement in net protein synthesis with higher protein intake. Regardless of the level of protein intake, the underlying alterations in protein metabolism that occurred as a response to burn injury persisted.

Adolescent↗
PubMed1982

Urea, glucose and alanine kinetics in man: effects of glucose infusion.

1. The simultaneous effects of an intravenous glucose infusion on plasma urea, glucose and alanine kinetics were investigated in normal post-absorptive man. 2. The primed constant intravenous infusion of compounds labelled with stable isotopes, [15N2]urea, [6-2H]glucose and [3-13C]alanine, was used. 3. The rate of appearance of glucose and urea in the plasma was rapidly reduced by the 17.7 mumol min-1 kg-1 glucose infusion. 4. In contrast, during the glucose infusion there was an increased rate of appearance of alanine in the plasma, and an increased percentage of glucose carbon atoms derived from alanine. 5. Reduced production of glucose and urea during the glucose infusion was not due to decreased gluconeogenesis from alanine.

Adult↗
PubMed1982

Mechanisms of insulin resistance following injury.

To assess the mechanisms of insulin resistance following injury, we examined the relationship between insulin levels and glucose disposal in nine nonseptic, multiple trauma patients (average age 32 years, Injury Severity Score 22) five to 13 days postinjury. Fourteen age-matched normals served as controls. Using a modification of the euglycemic insulin clamp technique, insulin was infused in 35 two-hour studies using at least one of four infusions rates (0.5, 1.0, 2.0 or 5.0 mU/kg min). Basal glucose levels were maintained by a variable infusion of 20% dextrose using bedside glucose monitoring and a servo-control algorithm. The amount of glucose infused reflected glucose disposal (M, mg/kg.min). Tracer doses of (6,6,2D2) glucose were administered in selected subjects to determine endogenous glucose production. At plasma insulin concentrations less than 100 microU/ml, responses in both groups were similar. However, maximal glucose disposal rates were significantly less in the patients than in the controls (9.17 +/- 0.87 mg/kg . min vs. 14.3 +/- 0.78, mean +/- SEM, p less than 0.01). Insulin clearance rates in the patients were almost twice that seen in controls. To further characterize this decrease in insulin responsiveness, we studied six additional patients and 12 controls following the acute elevation of glucose 125 mg/dl above basal (hyperglycemic glucose clamp). In spite of exaggerated endogenous insulin production in the patients (80-200 microU/ml vs. 30--70 in controls), M was significantly lower (6.23 +/- 0.59 vs. 9.46 +/- 0.79, p less than 0.02). In conclusion, this study demonstrated that (1) the maximal rate of glucose disposal is reduced in trauma patients; (2) the metabolic clearance rate of insulin in the injured patients is almost twice normal and; (3) insulin resistance following injury appears to occur in peripheral tissues, probably skeletal muscle, and is consistent with a postreceptor defect.

Adult↗
PubMed1982

Isotopic analysis of leucine and urea metabolism in exercising humans.

We have used the primed constant infusion of di-[15N]urea and [1-13C]leucine to determine the effects of mild exercise (approx 30% Vo2max for 105 min) on urea production and leucine metabolism in human subjects. The oxidation of plasma leucine was distinguished from the oxidation of leucine that never entered the plasma pool ("intracellular" leucine) by means of determining the enrichment of alpha-ketoisocaproic acid (alpha-KICA). Total leucine oxidation increased from 0.38 +/0 0.05 to 1.41 +/- 0.14 micromol . kg-1 . min-1 during exercise due to increases in the oxidation of plasma leucine (150%) and intracellular leucine (600%). Plasma leucine flux decreased slightly, but not significantly (0.1 greater than P greater than 0.05), and the percent of alpha-KICA derived from plasma leucine dropped significantly (P less than 0.05) from 79.5 +/- 4.3 at rest to 62.0 +/- 5.3% over the last 30 min of exercise. Despite the increase in leucine oxidation during exercise, urea concentration and production did not change. Thus in exercise urea production does not accurately reflect all aspects of amino acid metabolism.

Adult↗
PubMed1982

Leucine and urea metabolism in acute human cold exposure.

Four healthy males voluntarily underwent acute cold exposure at 10 degrees C. Metabolic rate doubled for the 100-min exposure. [1-13C]leucine and [15N2]urea were used as tracers of protein metabolism via a primed constant infusion. Total and plasma transported leucine oxidation approximately doubled, but the oxidation of leucine derived from protein in the tissue where oxidation occurred ("intracellular oxidation") did not change as it did when the same subjects underwent mild exercise. Rate of appearance of urea and leucine in plasma were not significantly different between control and cold. Although the rate of protein synthesis calculated from the leucine data did not change, the rate of catabolism increased. Net protein catabolism based on the urea data agreed well with the leucine data at rest but did not exhibit a significant increase during exposure. However, net protein catabolism based on the leucine data did increase significantly during acute cold exposure. Further, there appears to be a qualitative difference in the protein catabolism associated with the voluntary muscular activity of exercise and muscular shivering aimed at thermogenesis.

Blood Proteins↗
PubMed1982

Quantitative aspects of glucose production and metabolism in healthy elderly subjects.

The metabolic basis for the reduced glucose tolerance that occurs during aging in humans has been explored with the aid of a primed constant intravenous infusion method of labeled glucose (6-3H; 6,6,2H- and U-13C-glucose). Healthy young adult men and women (24 +/- 3 yr) and elderly men and women (75 +/- 4 yr) participated in a series of studies designed to quantify rates of plasma glucose appearance, oxidation, and recycling while subjects were in the postabsorptive (basal) state and to determine rates of hepatic glucose production and glucose disappearance in response to intravenous glucose at approximately 1 and 2 mg x kg-1min-1 and also 4 mg x kg-1min-1 without or with a simultaneous infusion of insulin to maintain normoglycemia. Basal rates of glucose production were 2.41 +/- 0.06 and 2.18 /+/- 0.05 mg x kg-1min-1 in the young adults and elderly, respectively (P less than 0.05). Recycling of glucose carbon and glucose oxidation rates did not differ significantly between the two age groups. Infusion of unlabeled glucose reduced hepatic glucose production to the same extent in the two groups, indicating that the mechanisms responsible for altered hepatic glucose production with intravenous glucose administration remain intact during human aging. Plasma insulin changes were similar in young adult and elderly subjects receiving 4 mg x kg-1min-1 unlabeled glucose except that the higher plasma glucose levels in the elderly were associated with higher insulin levels. For elderly subjects, the amount of exogenous insulin required to maintain normoglycemia at the 4 mg x kg-1min-1 glucose infusion rate was about twice that necessary in young adults.

Adult↗
PubMed1982

Effect of neonatal androgenization on the LHRH response of dispersed pituitary cell cultures.

To determine if neonatal androgenization affects pituitary luteinizing hormone releasing hormone (LHRH) response, female rats were androgenized 24-48 hr following birth. Intact male and female litter mates were maintained for comparison. At 83 days of age, randomly selected males and androgenized females were gonadectomized. At 90 days of age, pituitary cell cultures were begun. On day 3 the cells were challenged with LHRH. Gonadotropin response was determined by radioimmunoassay (RIA). Basal gonadotropin release from androgenized female cells was similar to male cells, while the pattern and magnitude of the LHRH response was similar to intact female cells. After castration, the pattern and magnitude of the LHRH response of the androgenized female pituitary was most like the male. Androgenized female cells exhibited mixed male and female LHRH response.

Animals↗
PubMed1982

Somatostatin infusion inhibits glucose production in burn patients.

The acute response to a continuous infusion of somatostatin (0.1-0.15 micrograms/kg min) for between 30 to 180 min in five burn patients was investigated. In all patients the somatostatin reduced both insulin and glucagon levels, and the glucagon was reduced to a greater extent (on a molar basis) than the insulin. In all cases, the rate of production of glucose measured by the primed-constant infusion of 6,6-D2-glucose was suppressed during the infusion. Plasma glucose concentration, however, did not change in a predictable manner. Glucose clearance was consistently depressed, and the magnitude of change in glucose clearance was directly correlated to the magnitude of the reduction in insulin concentration induced by the somatostatin infusion (P less than 0.01). In one additional study, insulin was infused during the somatostatin infusion in order to maintain the basal level of insulin throughout the infusion, thus creating a selective drop in glucagon concentration. In this case, glucose clearance did not fall and the plasma glucose concentration declined owing to the lower rate of glucose production. These results suggested that in burn patients hyperglucagonemia stimulates glucose production and that insulin is effective in enhancing glucose clearance.

Adult↗
PubMed1982

Stable isotope approaches for study of energy substrate metabolism.

Stable isotopes can be used to assess various aspects of energy metabolism. This paper reviews recent experiments in which we have used stable isotopes, either alone or in conjunction with radiolabeled isotopes, to investigate carbohydrate, fat, and protein metabolism in both animals and human subjects. The approaches described allow investigation of the interrelationships of substrate kinetics and oxidation in vivo in ways not possible with radiolabeled isotopes alone.

Animals↗
PubMed1982

Effect of thermal injury on energy metabolism, substrate kinetics, and hormonal concentrations.

We have used a chronic dog model to study the kinetic aspects of the metabolic response to thermal injury. In order to interpret the kinetic data in the context of the overall response to injury, we also determined certain cardiovascular parameters as well as selected hormonal concentrations. We used a paired study design: each animal was studied twice before injury and then at 5 and 7 days following injury. The burn was induced while the animals were deeply anesthetized with sodium pentobarbital (30-35 mg/kg) but all studies were done in awake, unrestrained dogs using tracer methodology and both radiolabeled and stable isotopes. The burn induced a hyperdynamic state, with significant elevations in cardiac output, heart rate, and metabolic rate. The free fatty acid (FFA), glycerol and glucose flux rates were all elevated, as was the rate of production of urea. The increase in resting metabolic rate was due to comparable increases in the rates of oxidation of carbohydrate, fat, and protein. We found the responses of this canine burn model to closely resemble the human response to injury, and thus this model will be useful as a tool to elucidate some of the mechanisms responsible for the response to injury.

Amino Acids↗
PubMed1982

Infant coarctation of the aorta. Alternatives to subclavian flap repair.

Three cases of infant coarctation that could not be repaired by subclavian flap aortoplasty were repaired by alternative techniques. The principles of subclavian flap were considered and its major advantages preserved: in one case by using a common carotid artery flap and in two cases by constructing a free subclavian artery patch graft. Both of these alternatives worked well and should be considered for repair of infant coarctation when the anatomy is unsuitable for subclavian flap aortoplasty.

Aorta↗
PubMed1981

Measurement of urea kinetics in vivo by means of a constant tracer infusion of di-15N-urea.

We have assessed the feasibility of studying urea metabolism in vivo in both steady state and nonsteady state situations by means of the primed constant infusion of di-15N-urea and the analysis of the resulting enrichment in plasma urea. Both hepatectomized dogs with known rates of urea infusion and intact dogs were studied. The enrichment of the bistrimethylsilyl derivative of urea was determined on a gas chromatograph-mass spectrometer. Selected ion monitoring was set for m/e 189 (M - 15), m/e 190 (A + 1), and m/e 191 (A + 2), thus enabling the calculation of the rate of urea production from nonrecycled NH3 (from A + 2 data) (Ra N), the rate of recycling of NH3 into urea (Ra R) (from A + 1 data), and thus the total rate of urea production (Ra N + Ra R). When urine collections were made, the incorporation of urea-N into protein was estimated from the difference between Ra N and urea excretion. We found that, in the steady state in a hepatectomized dog, the rate of appearance of urea can be determined accurately. In the nonsteady state in both hepatectomized and intact dogs, urea appearance could be estimated within +/- 20% in most situations. The only situation in which this was not the case was when we attempted to measure rapid changes in Ra R. Thus, within limits, this can be a useful technique enabling the quantitation of various aspects of urea metabolism.

Animals↗