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 ◽  
...  
1996 ◽  
Vol 270 (4) ◽  
pp. E552-E558 ◽  
Author(s):  
M. Oehri ◽  
R. Ninnis ◽  
J. Girard ◽  
F. J. Frey ◽  
U. Keller

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.


1994 ◽  
Vol 266 (3) ◽  
pp. F432-F438 ◽  
Author(s):  
E. J. Choi ◽  
J. Bailey ◽  
R. C. May ◽  
T. Masud ◽  
B. J. Maroni

To determine whether dietary protein restriction (LPD) causes protein catabolism in adriamycin nephrosis, nephrotic and control rats were paired by weight and gavage fed an 8.5% protein diet for 3 days (protocol 1) or 12 days (protocol 2). Fasting whole body protein turnover was then measured using a constant infusion of L-[1-14C]leucine. After 3 days of LPD, proteinuria decreased slightly and body weight did not change in either group. In contrast, leucine oxidation and urinary urea nitrogen excretion in nephrotic rats decreased by 18% and 37%, respectively (P < or = 0.05). After 12 days of LPD, weight loss did not differ between groups. In contrast to protocol 1, proteinuria decreased by 45% in nephrotic rats fed LPD for 12 days, and leucine oxidation rats increased to the level of control rats. Rates of whole body protein synthesis (PS) and degradation (PD) did not differ between nephrotic and control rats receiving LPD for 3 or 12 days, but were significantly lower than rates measured in rats fed 22% protein. We conclude that 1) proteinuria stimulates protein conservation even when dietary protein intake is restricted; 2) the decrease in amino acid oxidation was dependent on moderate proteinuria, since prolonged LPD ameliorated nephrosis and leucine oxidation rates increased to control levels; and 3) since weight loss and rates of whole body PS and PD in nephrotic and control animals were indistinguishable, moderate proteinuria did not increase protein catabolism.


1994 ◽  
Vol 266 (6) ◽  
pp. E936-E945 ◽  
Author(s):  
Y. Sakurai ◽  
X. J. Zhang ◽  
R. R. Wolfe

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.


2014 ◽  
Vol 117 (11) ◽  
pp. 1380-1387 ◽  
Author(s):  
Roupen Hatzakorzian ◽  
Dominique Shum-Tim ◽  
Linda Wykes ◽  
Ansgar Hülshoff ◽  
Helen Bui ◽  
...  

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.


2002 ◽  
Vol 97 (4) ◽  
pp. 943-951 ◽  
Author(s):  
Thomas Schricker ◽  
Linda Wykes ◽  
Leopold Eberhart ◽  
Ralph Lattermann ◽  
Louise Mazza ◽  
...  

Background The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg x kg(-1) x min(-1) glucose) and amino acids (0.02 ml x kg(-1) x min(-1) Travasol 10%, equivalent to approximately 2.9 g x kg(-1) x day(-1)). Methods Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by L-[1-(13)C]leucine and [6,6-(2)H(2) ]glucose. Results Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 micromol x kg(-1) x h(-1) ) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 micromol x kg(-1) x h(-1);P = 0.054). Conclusions Epidural blockade accentuates the stimulating effect of parenteral alimentation on whole body protein synthesis.


2004 ◽  
Vol 100 (4) ◽  
pp. 973-978 ◽  
Author(s):  
Thomas Schricker ◽  
Linda Wykes ◽  
Leopold Eberhart ◽  
Ralph Lattermann ◽  
Franco Carli

Background The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose. Methods Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg.kg(-1).min(-1) glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by L-[L-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured. Results Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused. Conclusion Epidural analgesia achieved with ropivacaine or morphine does not suppress the catabolic response to surgery, either under fasting conditions or in the presence of an energy supply.


2006 ◽  
Vol 105 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Francesco Donatelli ◽  
Thomas Schricker ◽  
Giovanni Mistraletti ◽  
Francisco Asenjo ◽  
Piervirgilio Parrella ◽  
...  

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.


1968 ◽  
Vol 22 (3) ◽  
pp. 443-453 ◽  
Author(s):  
Sanford H. Jackson ◽  
T. Elliott ◽  
T. Gero ◽  
F. Brown ◽  
G. Vritz

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