Response of protein synthesis in human skeletal muscle to insulin, assessed with L-[d5])phenylalanine

McNurlan, Margaret A.; Essén, P.; Thorell, Anders; Calder, Andrew A.; Anderson, Sharon; Ljungsqvist, O.; Wernerman, Jan; Garlick, Peter J.

doi:10.1016/0261-5614(92)90273-s

Cited by 4 publications

(5 citation statements)

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“…The current study further confirmed previous report by us (15,18) and others ( 17,(20)(21)(22)60 motes muscle protein synthesis (26)(27)(28)(29) probably by its effect at the posttranscriptional level (26,27). Recently, it has been reported that the insulin-induced stimulation of muscle protein synthesis takes place only in growing rats and not in fully grown rats (50).…”

Section: Discussionsupporting

confidence: 92%

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Nair¹,

Ford²,

Ekberg³

et al. 1995

J. Clin. Invest.

228

232

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To elucidate the mechanism of insulin's anticatabolic effect in humans, protein dynamics were evaluated in the wholebody, splanchnic, and leg tissues in six C-peptide-negative type I diabetic male patients in the insulin-deprived and insulin-treated states using two separate amino acid models (leucine and phenylalanine). L-(1-3C,'5N)leucine, L-(ring-2H5)phenylalanine, and L-(ring-2H2) tyrosine were infused intravenously, and isotopic enrichments of [1-3C, 5N]-leucine, (13C)leucine, ("3C)ketoisocaproate, (2H5)phenylalanine, [21H4] tyrosine, (2H2)tyrosine, and '3CO2 were measured in arterial, hepatic vein, and femoral vein samples.Whole-body leucine flux, phenylalanine flux, and tyrosine flux were decreased (< 0.01) by insulin treatment, indicating an inhibition of protein breakdown. Moreover, insulin decreased (< 0.05) the rates of leucine oxidation and leucine transamination (P < 0.01), but the percent rate of ketoisocaproate oxidation was increased by insulin (P < 0.01). Insulin also reduced (< 0.01) whole-body protein synthesis estimated from both the leucine model (nonoxidative leucine disposal) and the phenylalanine model (disposal of phenylalanine not accounted by its conversion to tyrosine). Regional studies demonstrated that changes in whole body protein breakdown are accounted for by changes in both splanchnic and leg tissues. The changes in whole-body protein synthesis were not associated with changes in skeletal muscle (leg) protein synthesis but could be accounted for by the splanchnic region. We conclude that though insulin decreases whole-body protein breakdown in patients with type I diabetes by inhibition of protein breakdown in splanchnic and leg tissues, it selectively decreases protein synthesis in splanchnic tissues, which accounted for the observed decrease in whole-body protein synthesis. Insulin also augmented anabolism by decreasing leucine transamination. (J. Clin. Invest. 1995. 95:2926-2937

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Section: Discussionsupporting

confidence: 92%

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Nair¹,

Ford²,

Ekberg³

et al. 1995

J. Clin. Invest.

228

232

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“…It is important to note that neither the biopsy nor the arteriovenous method directly assesses the labeling of the aminoacyl-tRNA precursor pool used for protein synthesis. However, when the labeling of the aminoacyl-tRNA pool has been evaluated using either the flooding bolus method in humans (45) or adult animals ( 15,16), or by direct measurements of aminoacyl-tRNA (17), physiologic hyperinsulinemia failed to stimulate protein synthesis, in contrast to insulin's action in young, rapidly growing animals (46,47).…”

Section: Discussionmentioning

confidence: 99%

Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms.

Fryburg¹,

Jahn²,

Hill³

et al. 1995

J. Clin. Invest.

228

137

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Insulin inhibits proteolysis in human muscle thereby increasing protein anabolism. In contrast, IGF-I promotes muscle protein anabolism principally by stimulating protein synthesis. As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alter the muscle's response to insulin and/or IGF-I, this study was designed to examine the effects of insulin and IGF-I on human muscle protein turnover during hyperaminoacidemia. We measured phenylalanine balance and [3HI -phenylalanine kinetics in both forearms of 22 postabsorptive adults during a continuous [3HIphenylalanine infusion.Measurements were made basally and at 3 and 6 h after beginning a systemic infusion of a balanced amino acid mixture that raised arterial phenylalanine concentration about twofold. Throughout the 6 h, 10 subjects received insulin locally (0.035 mU/min per kg) into one brachial artery while 12 other subjects were given intraaterial IGF-I (100 ng/min per kg) to raise insulin or IGF-I concentrations, respectively, in the infused arm. The contralateral arm in each study served as a simultaneous control for the effects of amino acids (aa) alone.Glucose uptake and lactate release increased in the insulin-and IGF-I-infused forearms (P < 0.01) but did not change in the contralateral (aa alone) forearm in either study. In the aa alone arm in both studies, hyperaminoacidemia reversed the postabsorptive net phenylalanine release by muscle to a net uptake (P < 0.025, for each) due to a stimulation of muscle protein synthesis. In the hormoneinfused arms, the addition of either insulin or IGF-I promoted greater positive shifts in phenylalanine balance than the aa alone arm (P < 0.01). With insulin, the enhanced anabolism was due to inhibition of protein degradation (P < 0.02), whereas IGF-I augmented anabolism by a further stimulation of protein synthesis above aa alone (P < 0.02). We conclude that: (a) hyperaminoacidemia specifically stimulates muscle protein synthesis; (b) insulin, even with hyperaminoacidemia, improves muscle protein balance solely by inhibiting proteolysis; and (c) hyperaminoacidemia combined with IGF-I enhances protein synthesis more

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“…At 0600 h the next morning, measurements of resting energy expenditure were undertaken, followed by blood sampling for determination of IGF-I levels, TNF ␣ , and HIV load. Muscle (25).…”

Section: Introductionmentioning

confidence: 99%

“…Measurement of muscle protein synthesis from the incorporation of a flooding amount of L -[ 2 H 5 ]phenylalanine has been described in detail previously (25). Frozen samples of plasma and muscle tissue were analyzed as follows.…”

Section: Introductionmentioning

confidence: 99%

“…The ions at m / z 106 and 109 of the n -heptafluorobutyryl derivative were monitored with a VG MD 800 quadrupole gas chromatography mass spectrometer (Fisons Instruments, Inc., Beverly, MA) in the splitless mode after electron ionization. With this instrument there is no need to adjust the measured enrichment for the size of the sample, as was necessary previously (25,26). The rate or muscle protein synthesis, k s expressed as the % of the protein pool synthesized per d, was calculated from the formula:…”

Section: Introductionmentioning

confidence: 99%

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Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

et al. 1997

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Response of protein synthesis in human skeletal muscle to insulin, assessed with L-[d5])phenylalanine

Cited by 4 publications

References 0 publications

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Protein dynamics in whole body and in splanchnic and leg tissues in type I diabetic patients.

Insulin and insulin-like growth factor-I enhance human skeletal muscle protein anabolism during hyperaminoacidemia by different mechanisms.

Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease.

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