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Increased whole body glutamine turnover in cancer is not related to net hindquarter glutamine release
Methods: A subcutaneous MCA-induced sarcoma model was used. Rats (+250gr, n = 40) were studied bearing a small (5-10% bw), a large (lo-20% bw) tumour load and their pair-fed controls (CON). Under anaesthesia a constant infusion of L-[3,4-3H]-GLN and L-[2,6-3H]-PHE was given. At steady state, hindquarter bloodflow and arterial and venous substrate concentrations and amino acid specific activity were measured to calculate GLN production, GLN consumption, GLN net release, protein synthesis and protein breakdown across the hindquarter. Whole body GLN and PHE production were simultaneously calculated. Results: No anorexia occurred. Carcass weight decreased slightly in the small tumour group and in the large tumour group. Arterial GLN levels decreased from 634 f 15 (CON) to 557 + 13 in the large tumour group but not in the small tumour group (611 + 13uM). Whole body GLN production increased in the large tumour group (15 + 2 vs 41 + 11, p < 0.01) whereas it did not change in the small tumour group (13 f 3 pmole~100 g bw-‘.min-‘).
IGF-1 decreased the activities of cathepsins (B, B+L) in a timedependent manner up to 48 h. mRNA levels of cathepsins B and L were not decreased by IGF-1. In conclusion, IGF-1 inhibits muscle protein degradation, and its anti-catabolic effect is associated with decrease of cathepsins (B, L) activities, which undergo a posttranslational control. IGF-I has an anti-catabolic action beside its anabolic effect on the muscle.
P.55 Reduced aldosterone urinary excretion in response to partial or total starvation. A. MuAoz, L. L/add, M. Garcia-Domingo, A. Oliva, G. FranchArcas, X. Guirao and A. Sitges-Serra. Surgical Research Unit, 1.M.I.M. Department of Surgery, Hospital Universitari de/ Mar, Barcelona, Spain. The expansion of the extracellular water compartment, often seen during TPN, may be related to the metabolic changes occurring during starvation. There are contradictory data on the aldosterone response to starvation. We set up the present study to investigate the aldosterone urinary excretion in two different experimental models of fasting. Thirty-six rabbits were randomly assigned to three groups: A) Control group (CG, n = 8) received chow and water ad libitum for 12 days (mean i sem; 1478 + 81 g and 2606 + 159ml, respectively); B) Chronic partial starvation group (ChS. n = 11) was provided with 25 g of chow and 250 ml of water per day during 20 days resulting in a 20% weight reduction: C) Acute total starvation group (AS, n = 20) received 2 g of chow and 250 ml of water per day for 12 days until a similar weight reduction was obtained. Serum biochemical parameters and 48 h urinary aldosterone were determined at the beginning, in the middle, and at the end of the study. Water, sodium, nitrogen, and weight balances were calculated throughout the study. One-factor ANOVA was used to compare mean values between groups. Group ChS and AS lost 556 * 103 and 620 f 88 g, respectively of their basal body weight. During the first 48 h of fasting urinary aldosterone was higher in ChS than in AS (104 + 15 vs 69 + 7 ng/day, P = 0.03) and ChS group showed higher water balances (-64 + 9 vs -95 f 8 ml/day, P = 0.03) and higher sodium balances (-2.7 * 1 vs -9.2 * 1 mmol/day, P = 0.007). Urinary aldosterone (167 + 15 ng/day) and water balance (42 f 12 ml/day). were higher in CG than in both groups of starvation (P = 0.0001). There was a positive correlation between 48 h urinary aldosterone and water balances during the whole period (? = 0.32, P = 0.0005), and a negative correlation with water clearance (? = 0.4, P = 0.0001). At the end of the study, ChS and AS groups had similar low aldosterone excretion compared with CG (56 f 12 vs 55 i 6 vs 255 f 39 @day, P = 0.0001). Conclusions: 1) Aldosterone urinary excretion is reduced in fasted rabbits; 2) Total starvation results in a more marked initial urinary aldosterone reduction than partial starvation; 3) Aldosterone excretion at the end of the starvation period, with the same weight reduction, was similarly reduced in both groups.
Table: In the small tumour group muscle glutamine production increased. In the large tumour group, however, muscle GLN turnover halved resulting in a decreased GLN release compared to the small tumour group. Although whole body PHE production increased in small and large tumour groups, muscle protein synthesis and breakdown remained unchanged (not shown).
CON Small Large M-W U; p < 0.05
Net 131 307 209
release +24 + 67= ?;49a
Conclusion: Small tumours induce a minimal increase of muscle GLN production with no apparent change in whole body GLN turnover. Although large tumours enhance whole body GLN tunover, muscle GLN production and protein turnover remain unchanged.
P.57 The effect of depletion on muscle amino acid concentration in cancer patients. R. van Doorn, R. R. W. J. van dir Hulst, J. M. H. van der Bee/r”. N. E. P. De&z. P. 8. Soeters and M. F. von
Meyenfeldt. Depaltments of Surgery and ‘Otorhinolaryngology - Head and Neck Surgery, University of Limburg, Maastricht, The Netherlands. Introduction: It is hypothesised that in cancer patients diminished glutamine availability may lead to impaired function of organ systems depending on glutamine. Diminished availability of glutamine may be caused by high glutamine utilisation in cancerous tissue and/or due to depletion. In this study we investigated whether glutamine concentration in muscle of cancer patients, with or without depletion, is decreased. Material: After informed consent muscle biopsies were obtained in 11 patients and 5 healthy volunteers. Depletion was defined as weight loss of more than 10% of body-weight in the last three months. After an overnight fast a biopsy of the tibialis anterior muscle was taken and immediately frozen in liquid nitrogen. The biopsies were kept at -80 “C until determination by high pressure liquid chromatography. Results: Glutamine, alanine and total amount of amino acids are shown in the Table.
P.56 Increased whole body glutamine turnover in cancer is not related to net hindquarter glutamine release. 1.de Blaauw, N. E. P. Deutz and M. F. von Meyenfeldt. Dept of Surgev, Netherlands.
Glutamine turnover Production Consumption 227 + 52 102+35 417t120a lOOf 204f55 43+33 YS CONa; data in nmof.lOOg bw-‘.mtn?.
BMC, Univ. Limburg, Maastricht, The
Muscle is the body’s major source for glutamine (GLN). Cancer cells need GLN for energy and rapid replication and hereby disturb normal GLN metabolism. Aim of this study was to see whether changes of whole body GLN tunover, induced by cancer, were matched with regional muscle GLN release and turnover.
GlutamIne Al&nine Total amino acids Depleted cancer patients (n = 5) 11.2?0.9 16iOP 41.6 f 6.0 Non-depleted c&er patients (n = 6) 103?19 0.2 32.4 f ‘I 3 10!3*0.7 2.2+04 33 7 + 2.2 Healthy volunleers (n = 5) Values are given in mean + SEM. mmollkg wet weight. Mann-Whitney U = n.s
15f
48
IGF-1 decreased the activities of cathepsins (B, B+L) in a timedependent manner up to 48 h. mRNA levels of cathepsins B and L were not decreased by IGF-1. In conclusion, IGF-1 inhibits muscle protein degradation, and its anti-catabolic effect is associated with decrease of cathepsins (B, L) activities, which undergo a posttranslational control. IGF-I has an anti-catabolic action beside its anabolic effect on the muscle.
P.55 Reduced aldosterone urinary excretion in response to partial or total starvation. A. MuAoz, L. L/add, M. Garcia-Domingo, A. Oliva, G. FranchArcas, X. Guirao and A. Sitges-Serra. Surgical Research Unit, 1.M.I.M. Department of Surgery, Hospital Universitari de/ Mar, Barcelona, Spain. The expansion of the extracellular water compartment, often seen during TPN, may be related to the metabolic changes occurring during starvation. There are contradictory data on the aldosterone response to starvation. We set up the present study to investigate the aldosterone urinary excretion in two different experimental models of fasting. Thirty-six rabbits were randomly assigned to three groups: A) Control group (CG, n = 8) received chow and water ad libitum for 12 days (mean i sem; 1478 + 81 g and 2606 + 159ml, respectively); B) Chronic partial starvation group (ChS. n = 11) was provided with 25 g of chow and 250 ml of water per day during 20 days resulting in a 20% weight reduction: C) Acute total starvation group (AS, n = 20) received 2 g of chow and 250 ml of water per day for 12 days until a similar weight reduction was obtained. Serum biochemical parameters and 48 h urinary aldosterone were determined at the beginning, in the middle, and at the end of the study. Water, sodium, nitrogen, and weight balances were calculated throughout the study. One-factor ANOVA was used to compare mean values between groups. Group ChS and AS lost 556 * 103 and 620 f 88 g, respectively of their basal body weight. During the first 48 h of fasting urinary aldosterone was higher in ChS than in AS (104 + 15 vs 69 + 7 ng/day, P = 0.03) and ChS group showed higher water balances (-64 + 9 vs -95 f 8 ml/day, P = 0.03) and higher sodium balances (-2.7 * 1 vs -9.2 * 1 mmol/day, P = 0.007). Urinary aldosterone (167 + 15 ng/day) and water balance (42 f 12 ml/day). were higher in CG than in both groups of starvation (P = 0.0001). There was a positive correlation between 48 h urinary aldosterone and water balances during the whole period (? = 0.32, P = 0.0005), and a negative correlation with water clearance (? = 0.4, P = 0.0001). At the end of the study, ChS and AS groups had similar low aldosterone excretion compared with CG (56 f 12 vs 55 i 6 vs 255 f 39 @day, P = 0.0001). Conclusions: 1) Aldosterone urinary excretion is reduced in fasted rabbits; 2) Total starvation results in a more marked initial urinary aldosterone reduction than partial starvation; 3) Aldosterone excretion at the end of the starvation period, with the same weight reduction, was similarly reduced in both groups.
Table: In the small tumour group muscle glutamine production increased. In the large tumour group, however, muscle GLN turnover halved resulting in a decreased GLN release compared to the small tumour group. Although whole body PHE production increased in small and large tumour groups, muscle protein synthesis and breakdown remained unchanged (not shown).
CON Small Large M-W U; p < 0.05
Net 131 307 209
release +24 + 67= ?;49a
Conclusion: Small tumours induce a minimal increase of muscle GLN production with no apparent change in whole body GLN turnover. Although large tumours enhance whole body GLN tunover, muscle GLN production and protein turnover remain unchanged.
P.57 The effect of depletion on muscle amino acid concentration in cancer patients. R. van Doorn, R. R. W. J. van dir Hulst, J. M. H. van der Bee/r”. N. E. P. De&z. P. 8. Soeters and M. F. von
Meyenfeldt. Depaltments of Surgery and ‘Otorhinolaryngology - Head and Neck Surgery, University of Limburg, Maastricht, The Netherlands. Introduction: It is hypothesised that in cancer patients diminished glutamine availability may lead to impaired function of organ systems depending on glutamine. Diminished availability of glutamine may be caused by high glutamine utilisation in cancerous tissue and/or due to depletion. In this study we investigated whether glutamine concentration in muscle of cancer patients, with or without depletion, is decreased. Material: After informed consent muscle biopsies were obtained in 11 patients and 5 healthy volunteers. Depletion was defined as weight loss of more than 10% of body-weight in the last three months. After an overnight fast a biopsy of the tibialis anterior muscle was taken and immediately frozen in liquid nitrogen. The biopsies were kept at -80 “C until determination by high pressure liquid chromatography. Results: Glutamine, alanine and total amount of amino acids are shown in the Table.
P.56 Increased whole body glutamine turnover in cancer is not related to net hindquarter glutamine release. 1.de Blaauw, N. E. P. Deutz and M. F. von Meyenfeldt. Dept of Surgev, Netherlands.
Glutamine turnover Production Consumption 227 + 52 102+35 417t120a lOOf 204f55 43+33 YS CONa; data in nmof.lOOg bw-‘.mtn?.
BMC, Univ. Limburg, Maastricht, The
Muscle is the body’s major source for glutamine (GLN). Cancer cells need GLN for energy and rapid replication and hereby disturb normal GLN metabolism. Aim of this study was to see whether changes of whole body GLN tunover, induced by cancer, were matched with regional muscle GLN release and turnover.
GlutamIne Al&nine Total amino acids Depleted cancer patients (n = 5) 11.2?0.9 16iOP 41.6 f 6.0 Non-depleted c&er patients (n = 6) 103?19 0.2 32.4 f ‘I 3 10!3*0.7 2.2+04 33 7 + 2.2 Healthy volunleers (n = 5) Values are given in mean + SEM. mmollkg wet weight. Mann-Whitney U = n.s
15f
48