Effects of infused amino acids on glucose production and utilization in healthy human subjects

Amino acids have been reported to increase endogenous glucose production in normal human subjects during hyperinsulinemia: however, controversy exists as to whether insulin-mediated glucose disposal is inhibited under these conditions. The effect of an amino acid infusion on glucose oxidation rate has so far not been determined. Substrate oxidation rates, endogenous glucose production, and [13C]glucose synthesis from [13C]bicarbonate were measured in six normal human subjects during sequential infusions of exogenous glucose and exogenous glucose with (n = 5) or without (n = 5) exogenous amino acids. Amino acids increased endogenous glucose production by 84% and [13C]glucose synthesis by 235%. Glucose oxidation estimated from indirect calorimetry decreased slightly after amino acids, but glucose oxidation estimated from [13C]glucose-13CO2 data was increased by 14%. It is concluded that gluconeogenesis is the major pathway of amino acid degradation. During amino acid administration, indirect calorimetry underestimates the true rate of glucose oxidation, whereas glucose oxidation calculated from the 13C enrichment of expired CO2 during [U-13C]glucose infusion does not. A slight stimulation of glucose oxidation during amino acid infusion, concomitant with an increased plasma insulin concentration, indicates that amino acids do not inhibit glucose oxidation.

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Amino acids do not suppress proteolysis in premature neonates

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.281.3.e472 ◽

2001 ◽

Vol 281 (3) ◽

pp. E472-E478 ◽

Cited By ~ 30

Author(s):

Brenda B. Poindexter ◽

Cheryl A. Karn ◽

Catherine A. Leitch ◽

Edward A. Liechty ◽

Scott C. Denne

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Glucose Production ◽

Essential Amino Acids ◽

Endogenous Glucose Production ◽

Full Term ◽

Term Neonates ◽

Premature Neonates ◽

Amino Acid Infusion ◽

Amino Acid Availability

To determine whether increased amino acid availability can reduce proteolysis in premature neonates and to assess the capacity of infants born prematurely to acutely increase the irreversible catabolism of the essential amino acids leucine (via oxidation) and phenylalanine (via hydroxylation to form tyrosine), leucine and phenylalanine kinetics were measured under basal conditions and in response to a graded infusion of intravenous amino acids (1.2 and 2.4 g · kg−1 · day−1) in clinically stable premature (∼32 wk gestation) infants in the 1st wk of life. In contrast to the dose-dependent suppression of proteolysis seen in healthy full-term neonates, the endogenous rates of appearance of leucine and phenylalanine (reflecting proteolysis) were unchanged in response to amino acids (297 ± 21, 283 ± 19, and 284 ± 31 μmol · kg−1 · h−1 for leucine and 92 ± 6, 92 ± 4, and 84 ± 7 μmol · kg−1 · h−1 for phenylalanine). Similar to full-term neonates, leucine oxidation (40 ± 5, 65 ± 6, and 99 ± 7 μmol · kg−1 · h−1) and phenylalanine hydroxylation (12 ± 1, 16 ± 1, and 20 ± 2 μmol · kg−1 · h−1) increased in a stepwise fashion in response to graded amino acids. This capacity to increase phenylalanine hydroxylation may be crucial to meet tyrosine needs when exogenous supply is limited. Finally, to determine whether amino acids stimulate glucose production in premature neonates, glucose rate of appearance was measured during each study period. In response to amino acid infusion, rates of endogenous glucose production were unchanged (and near zero).

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A Study of Relations between the Absorption of Amino Acids, Dipeptides, Water and Electrolytes in the Normal Human Jejunum

Clinical Science ◽

10.1042/cs0490401 ◽

1975 ◽

Vol 49 (5) ◽

pp. 401-408 ◽

Cited By ~ 3

Author(s):

D. B. A. Silk ◽

P. D. Fairclough ◽

Nicola J. Park ◽

Annette E. Lane ◽

Joan P. W. Webb ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Sodium Chloride ◽

Human Subjects ◽

Sodium Content ◽

Sodium Chloride Solutions ◽

Electrolyte Absorption ◽

Wide Range ◽

Osmotic Solution ◽

Normal Human

1. A double-lumen perfusion technique was used to study the effect of a wide range of concentrations of the dipeptide glycyl-l-alanine and its constituent amino acids on water and electrolyte absorption from iso-osmotic solutions in the upper jejunum of normal human subjects. 2. There was no significant absorption of water and electrolytes from sodium chloride solution (150 mmol/l) but the presence of the dipeptide or its constituent amino acids stimulated water and electrolyte absorption. 3. Water absorption reached a peak at increasing amino acid and dipeptide concentrations and then tailed off. Our data suggest that the tailing off is not solely due to the diminished sodium content of the solutions. 4. During perfusion of the dipeptide-sodium chloride and amino acid-sodium chloride solutions solute and water were absorbed as an iso-osmotic solution. Analysis of the results indicates that this could occur at high dipeptide concentrations only if the majority of the dipeptide enters the cell intact.

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

Journal of Applied Physiology ◽

10.1152/japplphysiol.00175.2014 ◽

2014 ◽

Vol 117 (11) ◽

pp. 1380-1387 ◽

Cited By ~ 5

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.

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

Anesthesiology ◽

10.1097/00000542-200608000-00007 ◽

2006 ◽

Vol 105 (2) ◽

pp. 253-259 ◽

Cited By ~ 18

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 < 0.05), with greater changes in the PCA group (P < 0.05). Administration of amino acids suppressed the appearance of leucine from protein breakdown in both groups (P < 0.05), although the decrease was greater in the PCA group (P < 0.05). Leucine oxidation increased in both groups (P < 0.05), with greater change in the epidural group (P < 0.05). Protein synthesis increased to the same extent in both groups (P < 0.05). Protein balance became positive after the infusion of amino acids, and the effect was greater in the PCA group (P < 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.

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Site of Insulin Resistance after Surgery: The Contribution of Hypocaloric Nutrition and Bed Rest

Clinical Science ◽

10.1042/cs0930137 ◽

1997 ◽

Vol 93 (2) ◽

pp. 137-146 ◽

Cited By ~ 71

Author(s):

Jonas Nygren ◽

Anders Thorell ◽

Suad Efendic ◽

K. Sree Nair ◽

Olle Ljungqvist

Keyword(s):

Insulin Resistance ◽

Glucose Oxidation ◽

Glucose Utilization ◽

Glucose Production ◽

Bed Rest ◽

Endogenous Glucose Production ◽

Whole Body ◽

Glucose Disposal ◽

Before And After ◽

Endogenous Glucose

1. Insulin resistance after surgery has been shown to be related to several important derangements in protein and fat metabolism. However, mechanisms of impaired glucose tolerance after surgery remain ill-defined. 2. Insulin sensitivity and glucose kinetics (6,62H2-glucose) were studied in seven patients before and after elective surgery (surgery group), by two step-hyperinsulinaemic (0.3 and 0.8 munits kg−1 min−1), normoglycaemic (4.5 mmol/l) clamps. Six healthy subjects were studied, using the same protocol, before and after a similar period of bed rest and hypocaloric nutrition (fast/bed rest group) to delineate the effects of surgery per se. 3. Basal endogenous glucose production and whole-body glucose disposal was higher after surgery (P < 0.001), whereas no change was found after fast/bed rest. During glucose clamps, the glucose infusion rates required to maintain normoglycaemia and whole-body glucose disposal decreased (P < 0.001) after surgery, while endogenous glucose production increased (P < 0.001). In the control subjects, levels of endogenous glucose production remained unchanged after fast/bed rest. In contrast, glucose infusion rates and whole-body glucose disposal during glucose clamps also decreased after fast/bed rest (P < 0.01). However, the relative decrease in both these parameters was greater after surgery compared with after fast/bed rest (P < 0.01). 4. After surgery, energy expenditure and fat oxidation increased (P < 0.001), whereas glucose oxidation decreased (P < 0.05). No significant change was found in glucose utilization postoperatively. After fast/bed rest, no change was found in energy expenditure. However, fat oxidation increased (P < 0.01), whereas glucose oxidation and glucose utilization decreased (P < 0.05). 5. In conclusion, impaired glucose tolerance develops after surgery as a result of decreased insulin-stimulated whole-body glucose disposal as well as increased endogenous glucose release. Despite the increase in endogenous glucose production, the reduction in endogenous glucose production with each elevation of insulin was unaffected by surgery. Perioperative bed rest and/or hypocaloric nutrition contribute to the decrease in insulin-stimulated whole-body glucose disposal in the postoperative state, whereas these factors have no effects on endogenous glucose production.

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