TNF directly stimulates glucose uptake and leucine oxidation and inhibits FFA flux in conscious dogs

1996 ◽  
Vol 270 (5) ◽  
pp. E864-E872 ◽  
Author(s):  
Y. Sakurai ◽  
X. J. Zhang ◽  
R. R. Wolfe
Keyword(s):  
Glucose Production ◽  
Baseline Period ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Constant Infusion ◽  
Direct Effects ◽  
Body Protein ◽  
Leucine Oxidation ◽  
Period 2 ◽  
Plasma Ffa

We tested the hypothesis that the metabolic changes in glucose, lipid, and protein metabolism seen during tumor necrosis factor (TNF) infusion were due to the increase in plasma glucagon concentration rather than to the direct effects of TNF. We employed a pancreatic clamp technique to keep plasma insulin and glucagon concentrations constant throughout a 4-h isotope infusion. Glucose, lipid, and protein kinetics were measured by means of the primed, constant infusion of [6,6-2H]glucose, [2H5]glycerol, [2H2]palmitic acid, and [1-13C]leucine. After a 2-h baseline period (period 1), TNF was infused as a primed, constant infusion (prime, 2.5 micrograms/kg; constant infusion, 62.5 ng.kg-1.min-1) for 2 h (period 2). Whereas plasma glucose concentration dropped significantly during TNF infusion, endogenous glucose production did not change. The decrease in glucose concentrations was due to a stimulation of glucose clearance (P < 0.05). The rate of lipolysis did not decrease significantly, but free fatty acid (FFA) flux and plasma FFA concentration significantly decreased during TNF infusion (P < 0.05). The rate of appearance of leucine was not affected by TNF infusion, but TNF caused a significant increase in 13CO2 excretion (P < 0.05) and leucine oxidation (P < 0.05). The calculated rates of whole body protein synthesis decreased. We concluded that TNF did not directly affect glucose production. Furthermore, changes in protein and lipid kinetics during TNF infusion were not mediated by changes in insulin or glucagon and may have reflected direct effects of TNF.

Postoperative Infusion of Amino Acids Induces a Positive Protein Balance Independently of the Type of Analgesia Used

2006 ◽  
Vol 105 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Francesco Donatelli ◽  
Thomas Schricker ◽  
Giovanni Mistraletti ◽  
Francisco Asenjo ◽  
Piervirgilio Parrella ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Epidural Analgesia ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Protein Balance ◽  
Body Protein ◽  
Leucine Oxidation ◽  
Endogenous Glucose

Background Net loss of body protein is a prominent feature of the catabolic response to surgical tissue trauma. Epidural analgesia with hypocaloric dextrose has been demonstrated to attenuate leucine oxidation but was unable to make protein balance positive. The current study was set to determine whether an infusion of amino acids on the second day after colon surgery would revert the catabolic state and promote protein synthesis while maintaining glucose homeostasis in patients receiving epidural analgesia as compared with patient-controlled analgesia with morphine (PCA). Methods Sixteen patients undergoing colorectal surgery were randomly assigned to receive epidural blockade or PCA as analgesic techniques and underwent a 6-h stable isotope infusion study (3 h fasted, 3 h fed) on the second postoperative day. Whole body glucose kinetics and protein turnover were measured using [6,6-2H2]glucose and l-[1-13C]leucine as tracer. Results The infusion of amino acids caused a decrease in endogenous glucose rate of appearance in both groups (P &lt; 0.05), with greater changes in the PCA group (P &lt; 0.05). Administration of amino acids suppressed the appearance of leucine from protein breakdown in both groups (P &lt; 0.05), although the decrease was greater in the PCA group (P &lt; 0.05). Leucine oxidation increased in both groups (P &lt; 0.05), with greater change in the epidural group (P &lt; 0.05). Protein synthesis increased to the same extent in both groups (P &lt; 0.05). Protein balance became positive after the infusion of amino acids, and the effect was greater in the PCA group (P &lt; 0.05). Conclusions Infusion of amino acids decreased the endogenous glucose production and induced a positive protein balance independent of the type of anesthesia provided, although such effects were greater in the PCA group.

Effect of tumor necrosis factor on substrate and amino acid kinetics in conscious dogs

1994 ◽  
Vol 266 (6) ◽  
pp. E936-E945 ◽  
Author(s):  
Y. Sakurai ◽  
X. J. Zhang ◽  
R. R. Wolfe
Keyword(s):  
Amino Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Glucose Production ◽  
Conscious Dogs ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Period 2 ◽  
Necrosis Factor

Two groups of conscious dogs were studied using isotopic tracer techniques to test the hypothesis that tumor necrosis factor (TNF) affects glucose production, lipolysis, amino acid, and protein kinetics. [1-13C]leucine, [15N2]urea, [6,6-2H2]glucose, and [2H5]glycerol were infused to determine the leucine, urea, glucose, and lipid kinetics, and NaH14CO3 was infused to determine the rate of CO2 production. In one group, after a 2-h basal period (period 1), recombinant human TNF was infused (prime, 2.5 micrograms/kg; constant, 62.5 ng.kg-1.min-1) for 2 h (period 2; group 1, n = 15). Group 2 received saline rather than TNF in period 2 (n = 3). TNF infusion caused a significant increase in endogenous glucose production, a significant increase in glucose clearance rate, and a decrease in glycerol flux. Although TNF infusion did not change leucine flux, leucine oxidation increased by 49% (P < 0.0001), and nonoxidative leucine disappearance decreased during TNF infusion by 13% (P < 0.0001). TNF infusion also caused a significant increase (18%) in endogenous urea production. TNF significantly increased plasma glucagon concentration. We conclude that TNF causes a shift toward carbohydrate metabolism and stimulates the oxidation of amino acids. Whereas whole body protein breakdown is not affected by TNF, protein synthesis is impaired, leading to an increase in net protein breakdown.

Glucose and insulin administration while maintaining normoglycemia inhibits whole body protein breakdown and synthesis after cardiac surgery

2014 ◽  
Vol 117 (11) ◽  
pp. 1380-1387 ◽  
Author(s):  
Roupen Hatzakorzian ◽  
Dominique Shum-Tim ◽  
Linda Wykes ◽  
Ansgar Hülshoff ◽  
Helen Bui ◽  
...  
Keyword(s):  
Amino Acids ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Control Group ◽  
Protein Breakdown ◽  
Body Protein ◽  
Cabg Surgery ◽  
Insulin Group ◽  
Endogenous Glucose

We investigated the effect of insulin administered as part of a hyperinsulinemic-normoglycemic clamp on protein metabolism after coronary artery bypass grafting (CABG) surgery. Eighteen patients were studied, with nine patients in the control group receiving standard metabolic care and nine patients receiving insulin (5 mU·kg−1·min−1). Whole body glucose production, protein breakdown, synthesis, and oxidation were determined using stable isotope tracer kinetics (l-[1-13C]leucine, [6,6-2H2]glucose) before and 6 h after the procedure. Plasma amino acids, cortisol, and lactate were also measured. Endogenous glucose production (preoperatively 10.0 ± 1.6, postoperatively 3.7 ± 2.5 μmol·kg−1·min−1; P = 0.0001), protein breakdown (preoperatively 105.3 ± 9.8, postoperatively 85.2 ± 9.2 mmol·kg−1·h−1; P = 0.0005) and synthesis (preoperatively 88.7 ± 8.7, postoperatively 72.4 ± 8.4 mmol·kg−1·h−1; P = 0.0005) decreased in the presence of hyperinsulinemia, whereas both parameters remained unchanged in the control group. A positive correlation between endogenous glucose production and protein breakdown was observed in the insulin group ( r2 = 0.385). Whole body protein oxidation and balance decreased after surgery in patients receiving insulin without reaching statistical significance. In the insulin group the plasma concentrations of 13 of 20 essential and nonessential amino acids decreased to a significantly greater extent than in the control group. In summary, supraphysiological hyperinsulinemia, while maintaining normoglycemia, decreased whole body protein breakdown and synthesis in patients undergoing CABG surgery. However, net protein balance remained negative.

scholarly journals Impact of Growth Hormone and Dehydroepiandrosterone on Protein Metabolism in Glucocorticoid-Treated Patients

2008 ◽  
Vol 93 (3) ◽  
pp. 688-695 ◽  
Author(s):  
Morton G. Burt ◽  
Gudmundur Johannsson ◽  
A. Margot Umpleby ◽  
Donald J. Chisholm ◽  
Ken K. Y. Ho
Keyword(s):  
Protein Metabolism ◽  
Dose Finding ◽  
Whole Body ◽  
Constant Infusion ◽  
Leucine Incorporation ◽  
Protein Loss ◽  
Body Protein ◽  
Prednisone Dose ◽  
Leucine Oxidation

Abstract Context: Chronic pharmacological glucocorticoid (GC) use causes substantial morbidity from protein wasting. GH and androgens are anabolic agents that may potentially reverse GC-induced protein loss. Objective: Our objective was to assess the effect of GH and dehydroepiandrosterone (DHEA) on protein metabolism in subjects on long-term GC therapy. Design: This was an open, stepwise GH dose-finding study (study 1), followed by a randomized cross-over intervention study (study 2). Setting: The studies were performed at a clinical research facility. Patients and Intervention: In study 1, six subjects (age 69 ± 4 yr) treated with long-term (&gt;6 months) GCs (prednisone dose 8.3 ± 0.8 mg/d) were studied before and after two sequential GH doses (0.8 and 1.6 mg/d) for 2 wk each. In study 2, 10 women (age 71 ± 3 yr) treated with long-term GCs (prednisone dose 5.4 ± 0.5 mg/d) were studied at baseline and after 2-wk treatment with GH 0.8 mg/d, DHEA 50 mg/d, or GH and DHEA (combination treatment). Main Outcome Measure: Changes in whole body protein metabolism were assessed using a 3-h primed constant infusion of 1-[13C]leucine, from which rates of leucine appearance, leucine oxidation, and leucine incorporation into protein were estimated. Results: In study 1, GH 0.8 and 1.6 mg/d significantly reduced leucine oxidation by 19% (P = 0.03) and 31% (P = 0.02), and increased leucine incorporation into protein by 10% (P = 0.13) and 19% (P = 0.04), respectively. The lower GH dose did not cause hyperglycemia, whereas GH 1.6 mg/d resulted in fasting hyperglycemia in two of six subjects. In study 2, DHEA did not significantly change leucine metabolism alone or when combined with GH. Blood glucose was not affected by DHEA. Conclusion: GH, at a modest supraphysiological dose of 0.8 mg/d, induces protein anabolism in chronic GC users without causing diabetes. DHEA 50 mg/d does not enhance the effect of GH. GH may safely prevent or reverse protein loss induced by chronic GC therapy.

Effects of growth hormone and IGF-I on glucocorticoid-induced protein catabolism in humans

1996 ◽  
Vol 270 (4) ◽  
pp. E552-E558 ◽  
Author(s):  
M. Oehri ◽  
R. Ninnis ◽  
J. Girard ◽  
F. J. Frey ◽  
U. Keller
Keyword(s):  
Growth Hormone ◽  
Plasma Concentrations ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Protein Catabolism ◽  
Body Protein ◽  
Glucose Clearance ◽  
Igf I ◽  
Endogenous Glucose

The effects of similar increases in total insulin-like growth factor I (IGF-I) plasma concentrations achieved by either recombinant human (rh) growth hormone (GH) or rhIGF-I administration on whole body protein and glucose kinetics were assessed. Twenty-six healthy subjects received methylprednisolone (0.5 mg.kg-1.day-1 orally) during 6 days in combination with either placebo (saline sc), GH (0.3 mg.kg-1.day-1 sc), or IGF-I (80 micrograms.kg-1.day-1 sc) in a double-blind randomized fashion. Glucocorticoid administration resulted in protein catabolism as indicated by an increase in leucine flux and a 62 +/- 13% increase in leucine oxidation ([1-13C]leucine infusion technique); this increase was abolished by GH (-1 +/- 18%) as was statistically insignificant during IGF-I treatment (+53 +/- 25%). GH increased endogenous glucose production by 28 +/- 8%, augmented glucocorticoid-induced insulin resistance of peripheral glucose clearance (euglycemic clamp), and increased circulating lipids. IGF-I administration resulted in both increased endogenous glucose production and increased peripheral glucose clearance such that plasma glucose concentrations remained unchanged by IGF-I. IGF-I lowered circulating GH and insulin and altered IGF binding proteins, which all may have reduced bioactivity of IGF-I. The data demonstrate that, in spite of similar total IGF-I plasma concentrations during treatment, GH and IGF-I exert markedly different effects on whole body leucine, glucose, and lipid metabolism.

scholarly journals Hyperinsulinemic-normoglycemic clamp administered together with amino acids induces anabolism after cardiac surgery

2016 ◽  
Vol 311 (6) ◽  
pp. R1085-R1092 ◽  
Author(s):  
Takumi Codère-Maruyama ◽  
Thomas Schricker ◽  
Dominique Shum-Tim ◽  
Linda Wykes ◽  
Evan Nitschmann ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Open Heart Surgery ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
High Dose ◽  
Protein Balance ◽  
Body Protein

Cardiac surgery triggers an inflammatory stress response, leading to protein catabolism, a process that even high-dose insulin therapy alone cannot reverse. To determine whether hyperinsulinemic-normoglycemic clamp and perioperative amino acid (AA) supplementation improves whole body protein balance, 20 patients scheduled for elective coronary artery bypass grafting surgery were randomly assigned to have intra- and postoperative hyperinsulinemic-normoglycemic clamp, with or without intravenous AA supplementation. Primed continuous infusions of [6,6-2H2]glucose and l-[1-13C]leucine were used to quantify whole body protein and glucose metabolism before and after surgery. Adipose tissue and serum cytokines were also analyzed to measure their responsiveness to the anabolic effect of AA administration. During hyperinsulinemic-normoglycemic clamp, AA supplementation successfully stimulated whole body protein synthesis, resulting in a positive whole body protein balance after surgery (insulin: −13.6 ± 4.5 vs. insulin + AA: 2.1 ± 5.4 μmol·kg−1·h−1, P < 0.001). Endogenous glucose production was equally suppressed in both groups (insulin: 0.0 ± 3.8 vs. insulin + AA 1.6 ± 1.6 μmol·kg−1·min−1, P = 0.230). AA supplementation led to significant changes in serum and tissue IL-6 (insulin: 246.6 ± 111.2 vs. insulin + AA: 124.5 ± 79.3 pg/ml, P = 0.011). In conclusion, hyperinsulinemic-normoglycemic clamp technique, together with AA supplementation, can induce an anabolic state after open-heart surgery, as quantified by a positive whole body protein balance.

Modulation of whole body protein metabolism, during and after exercise, by variation of dietary protein

1998 ◽  
Vol 85 (5) ◽  
pp. 1744-1752 ◽  
Author(s):  
J. L. Bowtell ◽  
G. P. Leese ◽  
K. Smith ◽  
P. W. Watt ◽  
A. Nevill ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dietary Protein ◽  
Whole Body ◽  
Constant Infusion ◽  
Body Protein ◽  
Leucine Oxidation ◽  
Low Protein ◽  
Branched Chain ◽  
Exercise Induced ◽  
Induced Changes

The aim of this study was to investigate dietary protein-induced changes in whole body leucine turnover and oxidation and in skeletal muscle branched chain 2-oxo acid dehydrogenase (BCOADH) activity, at rest and during exercise. Postabsorptive subjects received a primed constant infusion ofl-[1-13C,15N]leucine for 6 h, after previous consumption of a high- (HP; 1.8 g ⋅ kg−1 ⋅ day−1, n = 8) or a low-protein diet (LP; 0.7 g ⋅ kg−1 ⋅ day−1, n = 8) for 7 days. The subjects were studied at rest for 2 h, during 2-h exercise at 60% maximum oxygen consumption, then again for 2 h at rest. Exercise induced a doubling of both leucine oxidation from 20 μmol ⋅ kg−1 ⋅ h−1and BCOADH percent activation from 7% in all subjects. Leucine oxidation was greater before (+46%) and during (+40%, P < 0.05) the first hour of exercise in subjects consuming the HP rather than the LP diet, but there was no additional change in muscle BCOADH activity. The results suggest that leucine oxidation was increased by previous ingestion of an HP diet, attributable to an increase in leucine availability rather than to a stimulation of the skeletal muscle BCOADH activity.

scholarly journals Comparison of different techniques for estimating rates of protein synthesis in vivo in healthy and bacteraemic rats

1985 ◽  
Vol 226 (1) ◽  
pp. 37-42 ◽  
Author(s):  
J J Pomposelli ◽  
J D Palombo ◽  
K J Hamawy ◽  
B R Bistrian ◽  
G L Blackburn ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Rectus Muscle ◽  
Stochastic Modelling ◽  
Whole Body ◽  
Constant Infusion ◽  
Second Phase ◽  
Sprague Dawley ◽  
Body Protein ◽  
To Receive

Previous studies have reported that use of a flooding dose of radiolabelled amino acid is a more precise technique than the constant infusion of tracer quantities for determining rates of protein synthesis in rapidly turning-over tissues in the rat. However, there has been little direct investigation comparing different methods under comparable conditions. Initially, 12 healthy male Sprague-Dawley rats, weighing approx. 100 g, were randomized to receive either a bolus intravenous injection of 100 mumol of L-leucine (containing 30 microCi of [1-14C]leucine)/100 g body wt., or a continuous 2 h tracer infusion of [14C]leucine. In the second phase of the experiment, 12 additional rats were intravenously injected with 1 × 10(8) colony-forming units of Pseudomonas aeruginosa and 16 h later randomized to receive one of two infusions described above. Total protein synthesis as well as fractional synthesis rates were determined in liver, rectus muscle and whole body. Synthesis rates measured in liver, muscle and whole body were significantly higher in bacteraemic rats than in healthy rats. The flooding-dose methodology gave significantly higher estimates of protein synthesis in the liver, skeletal muscle and whole body than did the continuous-infusion method using direct measurement of the acid-soluble fraction from the respective tissue. Indirect estimates of whole-body protein synthesis based on plasma enrichments and stochastic modelling gave the lowest values.

scholarly journals The Greater Contribution of Gluconeogenesis to Glucose Production in Obesity Is Related to Increased Whole-Body Protein Catabolism

Diabetes ◽  
2006 ◽  
Vol 55 (3) ◽  
pp. 675-681 ◽  
Author(s):  
S. Chevalier ◽  
S. C. Burgess ◽  
C. R. Malloy ◽  
R. Gougeon ◽  
E. B. Marliss ◽  
...  
Keyword(s):  
Glucose Production ◽  
Whole Body ◽  
Protein Catabolism ◽  
Body Protein

scholarly journals Absorption and metabolism of glucose by the mesenteric-drained viscera of sheep fed on dried-grass or ground, maize-based diets

1985 ◽  
Vol 54 (2) ◽  
pp. 449-458 ◽  
Author(s):  
A. N. Janes ◽  
T. E. C. Weekes ◽  
D. G. Armstrong
Keyword(s):  
Small Intestine ◽  
Turnover Rate ◽  
Glucose Utilization ◽  
Venous Blood ◽  
Glucose Production ◽  
Glucose Absorption ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Glucose Turnover ◽  
Total Glucose

1. Sheep fitted with re-entrant canulas in the proximal duodenum and terminal ileum were used to determine the amount of α-glucoside entering, and apparently disappearing from, the small intestine when either dried-grass or ground maize-based diets were fed. The fate of any α-glucoside entering the small intestine was studied by comparing the net disappearance of such a-glucoside from the small intestine with the absorption of glucose into the mesenteric venous blood.2. Glucose absorption from the small intestine was measured in sheep equipped with catheters in the mesenteric vein and carotid artery. A continuous infusion of [6-3H]glucose was used to determine glucose utilization by the mesenteric-drained viscera and the whole-body glucose turnover rate (GTR).3. The amounts of α-glucoside entering the small intestine when the dried-grass and maize-based diets were given were 13.9 (SE 1.5) and 95.4 (SE 16.2) g/24 h respectively; apparent digestibilities of such α-glucoside in the small intestine were 60 and 90% respectively.4. The net absorption of glucose into the mesenteric venous blood was —2.03 (SE 1.20) and 19.28 (SE 0.75) mmol/h for the dried-grass and maize-based diets respectively. Similarly, total glucose absorption amounted to 1.52 (SE 1.35) and 23.33 (SE 1.86) mmol/h (equivalent to 7 and 101 g/24 h respectively). These values represented 83 and 11 1% of the a-glucoside apparently disappearing from the small intestine, determined using the re-entrant cannulated sheep.5. Total glucose absorption represented 8 and 61% of the whole-body GTR for the dried-grass and maize-based diets respectively. Endogenous glucose production was significantly lower when the sheep were fed on the maize-based diet compared with the dried-grass diet.6. The mesenteric-drained viscera metabolized a small amount of glucose, equivalent to 234 and 17% of the total glucose absorbed for the dried-grass and maize-based diets respectively.7. It is concluded that a large proportion of the starch entering the small intestine of sheep given a maize-based diet is digested and absorbed as glucose, and thus contributes to the whole-body GTR.

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