scholarly journals Increased plasma Gln and Leu Raand inappropriately low muscle protein synthesis rate in AIDS wasting

1998 ◽  
Vol 275 (4) ◽  
pp. E577-E583 ◽  
Author(s):  
Kevin E. Yarasheski ◽  
Jeffrey J. Zachwieja ◽  
Jennifer Gischler ◽  
Jan Crowley ◽  
Mary M. Horgan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Asymptomatic Group ◽  
Body Protein ◽  
Asymptomatic Subjects ◽  
Muscle Protein Synthesis Rate

Muscle protein wasting occurs in human immunodeficiency virus (HIV)-infected individuals and is often the initial indication of acquired immunodeficiency syndrome (AIDS). Little is known about the alterations in muscle protein metabolism that occur with HIV infection. Nine subjects with AIDS wasting (CD4 < 200/mm3), chronic stable opportunistic infections (OI), and ≥10% weight loss, fourteen HIV-infected men and one woman (CD4 > 200/mm3) without wasting or OI (asymptomatic), and six HIV-seronegative lean men (control) received a constant intravenous infusion of [1-13C]leucine (Leu) and [2-15N]glutamine (Gln). Plasma Leu and Gln rate of appearance (Ra), whole body Leu turnover, disposal and oxidation rates, and [13C]Leu incorporation rate into mixed muscle protein were assessed. Total body muscle mass/fat-free mass was greater in controls (53%) than in AIDS wasting (43%; P = 0.04). Fasting whole body proteolysis and synthesis rates were increased above control in the HIV+ asymptomatic group and in the AIDS-wasting group ( P = 0.009). Whole body Leu oxidation rate was greater in the HIV+ asymptomatic group than in the control and AIDS-wasting groups ( P < 0.05). Fasting mixed muscle protein synthesis rate was increased in the asymptomatic subjects (0.048%/h; P = 0.01) but was similar in AIDS-wasting and control subjects (0.035 vs. 0.037%/h). Plasma Gln Rawas increased in AIDS-wasting subjects but was similar in control and HIV+ asymptomatic subjects ( P < 0.001). These findings suggest that AIDS wasting results from 1) a preferential reduction in muscle protein, 2) a failure to sustain an elevated rate of mixed muscle protein synthesis while whole body protein synthesis is increased, and 3) a significant increase in Gln release into the circulation, probably from muscle. Several interesting explanations for the increased Gln Rain AIDS wasting exist.

Effect of growth hormone and resistance exercise on muscle growth in young men

1992 ◽  
Vol 262 (3) ◽  
pp. E261-E267 ◽  
Author(s):  
K. E. Yarasheski ◽  
J. A. Campbell ◽  
K. Smith ◽  
M. J. Rennie ◽  
J. O. Holloszy ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Treated Group ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Body Protein

The purpose of this study was to determine whether growth hormone (GH) administration enhances the muscle anabolism associated with heavy-resistance exercise. Sixteen men (21-34 yr) were assigned randomly to a resistance training plus GH group (n = 7) or to a resistance training plus placebo group (n = 9). For 12 wk, both groups trained all major muscle groups in an identical fashion while receiving 40 micrograms recombinant human GH.kg-1.day-1 or placebo. Fat-free mass (FFM) and total body water increased (P less than 0.05) in both groups but more (P less than 0.01) in the GH recipients. Whole body protein synthesis rate increased more (P less than 0.03), and whole body protein balance was greater (P = 0.01) in the GH-treated group, but quadriceps muscle protein synthesis rate, torso and limb circumferences, and muscle strength did not increase more in the GH-treated group. In the young men studied, resistance exercise with or without GH resulted in similar increments in muscle size, strength, and muscle protein synthesis, indicating that 1) the larger increase in FFM with GH treatment was probably due to an increase in lean tissue other than skeletal muscle and 2) resistance training supplemented with GH did not further enhance muscle anabolism and function.

Albumin and fibrinogen syntheses increase while muscle protein synthesis decreases in head-injured patients

1997 ◽  
Vol 273 (5) ◽  
pp. E898-E902 ◽  
Author(s):  
Odile Mansoor ◽  
Marc Cayol ◽  
Pierre Gachon ◽  
Yves Boirie ◽  
Pierre Schoeffler ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Albumin Synthesis ◽  
Body Protein ◽  
Head Injured ◽  
Injured Patients

The effect of trauma on protein metabolism was investigated in the whole body, muscle, and liver in severely head-injured patients presenting an acute inflammatory response by comparison to fed control subjects receiving a similar diet. Nonoxidative leucine disposal (an index of whole body protein synthesis) and muscle, albumin, and fibrinogen synthesis were determined by means of a primed, continuous infusion ofl-[1-13C]leucine. Nonoxidative leucine disposal increased by 28% in the patients ( P < 0.02). Fractional muscle protein synthesis rate decreased by 50% ( P < 0.01) after injury. Fractional and absolute fribrinogen synthesis rates were multiplied by two and nine, respectively, after injury ( P< 0.001). Albumin levels were lower in patients (25.2 ± 1.2 g/l, means ± SE) than in controls (33.7 ± 1.2 g/l, P < 0.001). However, fractional albumin synthesis rates were increased by 60% in patients (11.4 ± 1.0%/day) compared with controls (7.3 ± 0.4%/day, P < 0.01). Therefore, 1) head trauma induces opposite and large changes of protein synthesis in muscle and acute-phase hepatic proteins, probably mediated by cytokines, glucocorticoids, and other stress hormones, and 2) in these patients, hypoalbuminemia is not due to a depressed albumin synthesis.

Effect of testosterone on muscle mass and muscle protein synthesis

1989 ◽  
Vol 66 (1) ◽  
pp. 498-503 ◽  
Author(s):  
R. C. Griggs ◽  
W. Kingston ◽  
R. F. Jozefowicz ◽  
B. E. Herr ◽  
G. Forbes ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Muscle Mass ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Total Body Potassium ◽  
Body Protein ◽  
Total Body

We have studied the effect of a pharmacological dose of testosterone enanthate (3 mg.kg-1.wk-1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than 0.02); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than 0.0001). In four subjects, a primed continuous infusion protocol with L-[1–13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than 0.05). Leucine oxidation decreased slightly (17% mean decrease, P less than 0.01), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.

Leucine incorporation into mixed skeletal muscle protein in humans

1988 ◽  
Vol 254 (2) ◽  
pp. E208-E213 ◽  
Author(s):  
K. S. Nair ◽  
D. Halliday ◽  
R. C. Griggs
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Fiber Type ◽  
Whole Body ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Skeletal Muscle Protein ◽  
Body Protein

Fractional mixed skeletal muscle protein synthesis (FMPS) was estimated in 10 postabsorptive healthy men by determining the increment in the abundance of [13C]-leucine in quadriceps muscle protein during an intravenous infusion of L-[1-13C]leucine. FMPS in our subjects was 0.046 +/- 0.003%/h. Whole-body muscle protein synthesis (MPS) was calculated based on the estimation of muscle mass from creatinine excretion and compared with whole-body protein synthesis (WBPS) calculated from the nonoxidative portion of leucine flux. A significant correlation (r2 = 0.73, P less than 0.05) was found between MPS (44.7 +/- 3.4 mg.kg-1.h-1) and WBPS (167.8 +/- 8.5 mg.kg-1.h-1). The contribution of MPS to WBPS was 27 +/- 1%, which is comparable to the reports in other species. Morphometric analyses of adjacent muscle samples in eight subjects demonstrated that the biopsy specimens consisted of 86.5 +/- 2% muscular as opposed to other tissues. Because fiber type composition varies between biopsies, we examined the relationship between proportions of each fiber type and FMPS. Variation in the composition of biopsies and in fiber-type proportion did not affect the estimation of muscle protein synthesis rate. We conclude that stable isotope techniques using serial needle biopsies permit the direct measurement of FMPS in humans and that this estimation is correlated with an indirect estimation of WBPS.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review

2015 ◽  
Vol 173 (1) ◽  
pp. R25-R34 ◽  
Author(s):  
Jorn Trommelen ◽  
Bart B L Groen ◽  
Henrike M Hamer ◽  
Lisette C P G M de Groot ◽  
Luc J C van Loon
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Exogenous Insulin ◽  
Insulin Administration ◽  
Muscle Protein Synthesis Rate

BackgroundThough it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis ratesin vivoin humans.ObjectiveTo assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults.DesignA systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects.ConclusionsFrom the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50 000 pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults.

scholarly journals Reducing plasma HIV RNA improves muscle amino acid metabolism

2005 ◽  
Vol 288 (1) ◽  
pp. E278-E284 ◽  
Author(s):  
Kevin E. Yarasheski ◽  
Samuel R. Smith ◽  
William G. Powderly
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Hiv Rna ◽  
Muscle Protein Synthesis Rate

We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577–E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA (≥1 log) increased muscle protein synthesis rate and reduced Ra Gln and muscle proteasome activity in 10 men and 1 woman (22–57 yr, 60–108 kg, 17–33 kg muscle) with advanced HIV (CD4 = 0–311 cells/μl; HIV RNA = 10–375 × 103 copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/μl, P = 0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P = 0.003). Mixed muscle protein synthesis rate increased (0.062 ± 0.005 vs. 0.078 ± 0.006%/h, P = 0.01), Ra Gln decreased (387 ± 33 vs. 323 ± 15 μmol·kg fat-free mass−1·h−1, P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% ( P = 0.03). Muscle mass was only modestly increased (1 kg, P = not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, ∼3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.

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