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1.
Escobar J Frank JW Suryawan A Nguyen HV Kimball SR Jefferson LS Davis TA 《American journal of physiology. Endocrinology and metabolism》2005,288(5):E914-E921
Protein synthesis in skeletal muscle of adult rats increases in response to oral gavage of supraphysiological doses of leucine. However, the effect on protein synthesis of a physiological rise in plasma leucine has not been investigated in neonates, an anabolic population highly sensitive to amino acids and insulin. Therefore, in the current study, fasted pigs were infused intra-arterially with leucine (0, 200, or 400 micromol.kg(-1).h(-1)), and protein synthesis was measured after 60 or 120 min. Protein synthesis was increased in muscle, but not in liver, at 60 min. At 120 min, however, protein synthesis returned to baseline levels in muscle but was reduced below baseline values in liver. The increase in protein synthesis in muscle was associated with increased plasma leucine of 1.5- to 3-fold and no change in plasma insulin. Leucine infusion for 120 min reduced plasma essential amino acid levels. Phosphorylation of eukaryotic initiation factor (eIF)-4E-binding protein-1 (4E-BP1), ribosomal protein (rp) S6 kinase, and rpS6 was increased, and the amount of eIF4E associated with its repressor 4E-BP1 was reduced after 60 and 120 min of leucine infusion. No change in these biomarkers of mRNA translation was observed in liver. Thus a physiological increase in plasma leucine stimulates protein synthesis in skeletal muscle of neonatal pigs in association with increased eIF4E availability for eIF4F assembly. This response appears to be insulin independent, substrate dependent, and tissue specific. The results suggest that the branched-chain amino acid leucine can act as a nutrient signal to stimulate protein synthesis in skeletal muscle of neonates. 相似文献
2.
A method was developed for isolation of native ribosomal subunits from rat gastrocnemius muscle. Native 40 S subunits which were isolated by this method retained their associated nonribosomal proteins and consisted primarily of particles with equilibrium densities of 1.41 and 1.48 g/cm3. Based on the binding of radiolabeled Met-tRNAmeti, the 1.41 g/cm3 particle was identified as the 40 S initiation complex. Insulin deficiency in vivo resulting from either diabetes or fasting led to a 2-fold increase in 75 S monomers but had no effect on the numbers of native 40 and 60 S subunits or the relative distribution of the 1.41 and 1.48 g/cm3 particles. The rate of protein synthesis in perfused muscle preparations derived from insulin-deficient rats was reduced to about half the control value. Addition of insulin to the perfusate restored protein synthesis and 75 S monomers to control levels. The effect of insulin on protein synthesis was associated with a 1.5-fold increase in the amount of Met-tRNAmeti bound to the 1.41 g/cm3 particle. These findings identify formation of 40 S initiation complexes as a site of action of insulin on protein synthesis in skeletal muscle. 相似文献
3.
Orellana RA Jeyapalan A Escobar J Frank JW Nguyen HV Suryawan A Davis TA 《American journal of physiology. Endocrinology and metabolism》2007,293(5):E1416-E1425
In skeletal muscle of adults, sepsis reduces protein synthesis by depressing translation initiation and induces resistance to branched-chain amino acid stimulation. Normal neonates maintain a high basal muscle protein synthesis rate that is sensitive to amino acid stimulation. In the present study, we determined the effect of amino acids on protein synthesis in skeletal muscle and other tissues in septic neonates. Overnight-fasted neonatal pigs were infused with endotoxin (LPS, 0 and 10 microg.kg(-1).h(-1)), whereas glucose and insulin were maintained at fasting levels; amino acids were clamped at fasting or fed levels. In the presence of fasting insulin and amino acids, LPS reduced protein synthesis in longissimus dorsi (LD) and gastrocnemius muscles and increased protein synthesis in the diaphragm, but had no effect in masseter and heart muscles. Increasing amino acids to fed levels accelerated muscle protein synthesis in LD, gastrocnemius, masseter, and diaphragm. LPS stimulated protein synthesis in liver, lung, spleen, pancreas, and kidney in fasted animals. Raising amino acids to fed levels increased protein synthesis in liver of controls, but not LPS-treated animals. The increase in muscle protein synthesis in response to amino acids was associated with increased mTOR, 4E-BP1, and S6K1 phosphorylation and eIF4G-eIF4E association in control and LPS-infused animals. These findings suggest that amino acids stimulate skeletal muscle protein synthesis during acute endotoxemia via mTOR-dependent ribosomal assembly despite reduced basal protein synthesis rates in neonatal pigs. However, provision of amino acids does not further enhance the LPS-induced increase in liver protein synthesis. 相似文献
4.
O'Connor PM Bush JA Suryawan A Nguyen HV Davis TA 《American journal of physiology. Endocrinology and metabolism》2003,284(1):E110-E119
Infusion of physiological levels of insulin and/or amino acids reproduces the feeding-induced stimulation of muscle protein synthesis in neonates. To determine whether insulin and amino acids independently stimulate skeletal muscle protein synthesis in neonates, insulin secretion was blocked with somatostatin in fasted 7-day-old pigs (n = 8-12/group) while glucose and glucagon were maintained at fasting levels and insulin was infused to simulate either less than fasting, fasting, intermediate, or fed insulin levels. At each dose of insulin, amino acids were clamped at either the fasting or fed level; at the highest insulin dose, amino acids were also reduced to less than fasting levels. Skeletal muscle protein synthesis was measured using a flooding dose of l-[4-(3)H]phenylalanine. Hyperinsulinemia increased protein synthesis in skeletal muscle during hypoaminoacidemia and euaminoacidemia. Hyperaminoacidemia increased muscle protein synthesis during hypoinsulinemia and euinsulinemia. There was a dose-response effect of both insulin and amino acids on muscle protein synthesis. At each insulin dose, hyperaminoacidemia increased muscle protein synthesis. The effects of insulin and amino acids on muscle protein synthesis were largely additive until maximal rates of protein synthesis were achieved. Amino acids enhanced basal protein synthesis rates but did not enhance the sensitivity or responsiveness of muscle protein synthesis to insulin. The results suggest that insulin and amino acids independently stimulate protein synthesis in skeletal muscle of the neonate. 相似文献
5.
Vary TC Jefferson LS Kimball SR 《American journal of physiology. Endocrinology and metabolism》2001,281(5):E1045-E1053
Induction of sepsis in rats causes an inhibition of protein synthesis in skeletal muscle that is resistant to the stimulatory actions of insulin. To gain a better understanding of the underlying reason for this lack of response, the present study was undertaken to investigate sepsis-induced alterations in insulin signaling to regulatory components of mRNA translation. Experiments were performed in perfused hindlimb preparations from rats 5 days after induction of a septic abscess. Sepsis resulted in a 50% reduction in protein synthesis in the gastrocnemius. Protein synthesis in muscles from septic rats, but not controls, was unresponsive to stimulation by insulin. The insulin-induced hyperphosphorylation response of the translation repressor protein 4E-binding protein 1 (4E-BP1) and of the 70-kDa S6 kinase (S6K1) (1), two targets of insulin action on mRNA translation, was unimpaired in gastrocnemius of septic rats. Hyperphosphorylation of 4E-BP1 in response to insulin resulted in its dissociation from the inactive eukaryotic initiation factor (eIF)4E. 4E-BP1 complex in both control and septic rats. However, assembly of the active eIF4F complex as assessed by the association of eIF4E with eIF4G did not follow the pattern predicted by the increased availability of eIF4E resulting from changes in the phosphorylation of 4E-BP1. Indeed, sepsis caused a dramatic reduction in the amount of eIF4G associated with eIF4E in the presence or absence of insulin. Thus the inability of insulin to stimulate protein synthesis during sepsis may be related to a defect in signaling to a step in translation initiation involved in assembly of an active eIF4F complex. 相似文献
6.
The possible involvement of prostaglandin F2 alpha in the stimulation of muscle protein synthesis by insulin 总被引:8,自引:0,他引:8
The addition of insulin (8 ng/ml) in vitro to muscles from fasted rabbits increased protein synthesis (+80%) to a value similar to that found in muscles from fed donors. The addition of either indomethacin or meclofenamate completely blocked this effect of insulin. Muscles from fasted rabbits released less prostaglandin (PG)F2 alpha into the medium and the presence of insulin increased and indomethacin and meclofenamate reduced PGF2 alpha release. Other conditions (work load and leucocyte pyrogen) which increase protein synthesis in muscle also stimulate PGF2 alpha release. As both arachidonic acid and PGF2 alpha in themselves increase protein synthesis we suggest that accelerated phospholipolysis and PG synthesis have a general role in the control of muscle protein turnover. 相似文献
7.
Frank JW Escobar J Suryawan A Nguyen HV Kimball SR Jefferson LS Davis TA 《American journal of physiology. Endocrinology and metabolism》2006,290(2):E225-E233
Protein synthesis and eukaryotic initiation factor (eIF) activation are increased in muscle and liver of pigs parenterally infused with amino acids and insulin. To examine the effects of enteral protein and carbohydrate on protein synthesis, pigs (n = 42, 1.7 kg body wt) were fed isocaloric milk diets containing three levels of protein (5, 15, and 25 g x kg body wt(-1) x day(-1)) and two levels of lactose (low = 11 and high = 23 g x kg body wt(-1) x day(-1)) from 1 to 6 days of age. On day 7, pigs were gavage fed after 4-h food deprivation, and tissue protein synthesis rates and biomarkers of mRNA translation were assessed. Piglet growth and protein synthesis rates in muscle and liver increased with dietary protein and plateaued at 15 g x kg body wt(-1) x day(-1) (P < 0.001). Growth tended to be greater in high-lactose-fed pigs (P = 0.07). Plasma insulin was lowest in pigs fed 5 g x kg body wt(-1) x day(-1) protein (P < 0.0001). Plasma branched-chain amino acids increased as protein intake increased (P < 0.0001). Muscle (P < 0.001) and liver (P < or = 0.001) ribosomal protein S6 kinase-1 and eIF4E-binding protein phosphorylation increased with protein intake and plateaued at 15 g x kg body wt(-1) x day(-1). The results indicate that growth and protein synthesis rates in neonatal pigs are influenced by dietary protein and lactose intake and might be mediated by plasma amino acids and insulin levels. However, feeding protein well above the piglet's requirement does not further stimulate the activation of translation initiation or protein synthesis in skeletal muscle and liver. 相似文献
8.
Davis TA Fiorotto ML Burrin DG Vann RC Reeds PJ Nguyen HV Beckett PR Bush JA 《American journal of physiology. Endocrinology and metabolism》2002,283(4):E638-E647
Studies have shown that protein synthesis in skeletal muscle of neonatal pigs is uniquely sensitive to a physiological rise in both insulin and amino acids. Protein synthesis in cardiac muscle, skin, and spleen is responsive to insulin but not amino acid stimulation, whereas in the liver, protein synthesis responds to amino acids but not insulin. To determine the response of protein synthesis to insulin-like growth factor I (IGF-I) in this model, overnight-fasted 7- and 26-day-old pigs were infused with IGF-I (0, 20, or 50 microg. kg(-1). h(-1)) to achieve levels within the physiological range, while amino acids and glucose were clamped at fasting levels. Because IGF-I infusion lowers circulating insulin levels, an additional group of high-dose IGF-I-infused pigs was also provided replacement insulin (10 ng. kg(-0.66). min(-1)). Tissue protein synthesis was measured using a flooding dose of L-[4-(3)H]phenylalanine. In 7-day-old pigs, low-dose IGF-I increased protein synthesis by 25-60% in various skeletal muscles as well as in cardiac muscle (+38%), skin (+24%), and spleen (+32%). The higher dose of IGF-I elicited no further increase in protein synthesis above that found with the low IGF-I dose. Insulin replacement did not alter the response of protein synthesis to IGF-I in any tissue. The IGF-I-induced increases in tissue protein synthesis decreased with development. IGF-I infusion, with or without insulin replacement, had no effect on protein synthesis in liver, jejunum, pancreas, or kidney. Thus the magnitude, tissue specificity, and developmental change in the response of protein synthesis to acute physiological increases in plasma IGF-I are similar to those previously observed for insulin. This study provides in vivo data indicating that circulating IGF-I and insulin act on the same signaling components to stimulate protein synthesis and that this response is highly sensitive to stimulation in skeletal muscle of the neonate. 相似文献
9.
Wilson FA Orellana RA Suryawan A Nguyen HV Jeyapalan AS Frank J Davis TA 《American journal of physiology. Endocrinology and metabolism》2008,295(1):E187-E194
Chronic treatment of growing pigs with porcine somatotropin (pST) promotes protein synthesis and doubles postprandial levels of insulin, a hormone that stimulates translation initiation. This study aimed to determine whether the pST-induced increase in skeletal muscle protein synthesis was mediated through an insulin-induced stimulation of translation initiation. After 7-10 days of pST (150 microg x kg(-1) x day(-1)) or control saline treatment, pancreatic glucose-amino acid clamps were performed in overnight-fasted pigs to reproduce 1) fasted (5 microU/ml), 2) fed control (25 microU/ml), and 3) fed pST-treated (50 microU/ml) insulin levels while glucose and amino acids were maintained at baseline fasting levels. Fractional protein synthesis rates and indexes of translation initiation were examined in skeletal muscle. Effectiveness of pST treatment was confirmed by reduced urea nitrogen and elevated insulin-like growth factor I levels in plasma. Skeletal muscle protein synthesis was independently increased by both insulin and pST. Insulin increased the phosphorylation of protein kinase B and the downstream effectors of the mammalian target of rapamycin, ribosomal protein S6 kinase, and eukaryotic initiation factor (eIF)4E-binding protein-1 (4E-BP1). Furthermore, insulin reduced inactive 4E-BP1.eIF4E complex association and increased active eIF4E.eIF4G complex formation, indicating enhanced eIF4F complex assembly. However, pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of skeletal muscle protein synthesis in growing pigs is independent of the insulin-associated activation of translation initiation. 相似文献
10.
Protein synthesis was measured in perfused rat skeletal muscle using [14C]lysine in the presence of increasing amounts of lysine in the perfusate. The results obtained clearly indicated that both the extracellular and intracellular pools of amino acids act as direct precursors for protein synthesis and analysis of the data, according to O'Hara et al. (J. molec. cell. Cardiol. 13, 925-940, 1981) further indicated that extracellular sources of lysine supplied 64 and 81% of the lysine incorporated in the absence and presence of insulin, respectively. The rate of protein synthesis were assessed to be 0.22 mumol lysine incorporated g-1 muscle per 3 hr of perfusion increasing to 1.0 mumol g-1 3 hr-1 in the presence of insulin. 相似文献
11.
Wilson FA Suryawan A Orellana RA Nguyen HV Jeyapalan AS Gazzaneo MC Davis TA 《American journal of physiology. Endocrinology and metabolism》2008,295(4):E876-E883
Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were maintained at fasting levels. This study aimed to determine whether the pST-induced increase in insulin promotes skeletal muscle protein synthesis when amino acids are provided at fed levels and whether the response is associated with enhanced translation initiation factor activation. Growing pigs were treated with pST (0 or 180 microg x kg(-1) x day(-1)) for 7 days, and then pancreatic-glucose-amino acid clamps were performed. Amino acids were raised to fed levels in the presence of either fasted or fed insulin concentrations; glucose was maintained at fasting throughout. Muscle protein synthesis was increased by pST treatment and by amino acids (with or without insulin) (P<0.001). In pST-treated pigs, fed, but not fasting, amino acid concentrations further increased muscle protein synthesis rates irrespective of insulin level (P<0.02). Fed amino acids, with or without raised insulin concentrations, increased the phosphorylation of S6 kinase (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein 1 (4EBP1), decreased inactive 4EBP1.eIF4E complex association, and increased active eIF4E.eIF4G complex formation (P<0.02). pST treatment did not alter translation initiation factor activation. We conclude that the pST-induced stimulation of muscle protein synthesis requires fed amino acid levels, but not fed insulin levels. However, under the current conditions, the response to amino acids is not mediated by the activation of translation initiation factors that regulate mRNA binding to the ribosomal complex. 相似文献
12.
Ippei Yamaoka Masako Doi Mitsuo Nakayama Kanae Oba Fumiaki Yoshizawa 《Biochemical and biophysical research communications》2009,386(1):252-6142
Amino acid (AA) administration can stimulate heat accumulation in the body, as especially found under anesthetic conditions. To test our hypothesis that marked rise in plasma insulin concentrations following AA administration plays an important role in the heat storage, we intravenously administered either a balanced AA mixture or saline over 3 h, both with and without a primed-constant infusion of somatostatin in propofol-anesthetized rats. Rats on AA but lacking marked rise in plasma insulin by somatostatin treatment failed to show: attenuation of fall in core body temperature; partial increases in oxygen consumption; and stimulated muscle protein synthesis. Furthermore, the AA’s stimulatory effects on phosphorylation of mTOR, 4E-BP1, and S6K1 were partially blocked by somatostatin. Our findings strongly suggest that the marked rise in insulin following AA administration promote translation initiation activities and stimulate muscle protein synthesis, which facilitates heat accumulation in the body. 相似文献
13.
J Schwartz J Wiesen B Carlson L Yamasaki M Moore M Womble 《Canadian journal of physiology and pharmacology》1986,64(2):199-205
Skeletal muscle regenerates following grafting, but little is known about protein synthesis and its regulation during regeneration. We determined the sequence of changes in protein synthesis in rat extensor digitorum longus (EDL) muscle by the measurement of phenylalanine (Phe) incorporation into muscle protein at various times after grafting. Compared with control EDL, Phe incorporation in grafts doubled in 1 day, was four- to eight-fold greater from days 2 to 10 after grafting, and then subsided. Tissue mass (wet weight) increased rapidly from days 7 to 20 in EDL grafts. The maximal increase in protein synthesis occurred 7-10 days after grafting, whether or not the nerve was left intact. Autoradiography indicated that incorporated radioactivity was associated with regenerating muscle fibers on day 10. Deficiencies of insulin, pituitary or testicular hormones, or chronic in vivo administration of insulin, growth hormone, testosterone, or tri-iodothyronine did not substantially alter the elevation in incorporation of the Phe into muscle protein 10 days after grafting. The breakdown of EDL protein, measured in vitro simultaneously with protein synthesis, was increased five-fold, and overall protein degradation was elevated six-fold 10 days after grafting. These findings indicate that Phe incorporation is rapidly elevated following grafting of the EDL, and that by days 7-10 reflects synthesis in regenerating muscle fibers. The increase in protein synthesis associated with muscle regeneration at this time appears to be independent of innervation and anabolic hormones. 相似文献
14.
Protein synthesis in skeletal muscle of the perfused rat hemicorpus compared with rates in the intact animal. 总被引:8,自引:8,他引:0
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The rate of protein synthesis was measured in muscles of the perfused rat hemicorpus, and values were compared with rates obtained in whole animals. In gastrocnemius muscle of fed rats the rate of synthesis measured in the hemicorpus was the same as that in the whole animal. However, in plantaris, quadriceps and soleus muscles rates were higher in the hemicorpus than those in vivo. In the hemicorpus, starvation for 1 day decreased the rate of protein synthesis in gastrocnemius and plantaris muscles, in parallel with decreases in the RNA content, but the soleus remained unaffected. Similar effects of starvation were observed in vivo, so that the relationships between rates in vivo and in the hemicorpus were the same as those in fed rats. Proteins of quadriceps and plantaris muscles were separated into sarcoplasmic and myofibrillar fractions. The rate of synthesis in the sarcoplasmic fraction of the hemicorpus from fed rats was similar to that in vivo, but synthesis in the myofibrillar fraction was greater. In the plantaris of starved rats the rates of synthesis in both fractions were lower, but the relationships between rates measured in vivo and in the perfused hemicorpus were similar to those seen in fed rats. The addition of insulin to the perfusate of the hemicorpus prepared from 1-day-starved animals increased the rates of protein synthesis per unit of RNA in gastrocnemius and plantaris muscles to values above those seen in fed animals when measured in vivo or in the hemicorpus. Insulin had no effect on the soleus. Overall, the rates of protein synthesis in the hemicorpus differed from those in vivo. However, the effect of starvation when measured in the whole animal was very similar to that measured in the isolated rat hemicorpus when insulin was omitted from the perfusate. 相似文献
15.
Balage M Sinaud S Prod'homme M Dardevet D Vary TC Kimball SR Jefferson LS Grizard J 《American journal of physiology. Endocrinology and metabolism》2001,281(3):E565-E574
The respective roles of insulin and amino acids in regulation of skeletal muscle protein synthesis and degradation after feeding were examined in rats fasted for 17 h and refed over 1 h with either a 25 or a 0% amino acid/protein meal. In each nutritional condition, postprandial insulin secretion was either maintained (control groups: C(25) and C(0)) or blocked with diazoxide injections (diazoxide groups: DZ(25) and DZ(0)). Muscle protein metabolism was examined in vitro in epitrochlearis muscles. Only feeding the 25% amino acid/protein meal in the presence of increased plasma insulin concentration (C(25) group) stimulated protein synthesis and inhibited proteolysis in skeletal muscle compared with the postabsorptive state. The stimulation of protein synthesis was associated with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1), reduced binding of eIF4E to 4E-BP1, and increased assembly of the active eIF4E. eIF4G complex. The p70 S6 kinase (p70(S6k)) was also hyperphosphorylated in response to the 25% amino acid/protein meal. Acute postprandial insulin deficiency induced by diazoxide injections totally abolished these effects. Feeding the 0% amino acid/protein meal with or without postprandial insulin deficiency did not stimulate muscle protein synthesis, reduce proteolysis, or regulate initiation factors and p70(S6k) compared with fasted rats. Taken together, our results suggest that both insulin and amino acids are required to stimulate protein synthesis, inhibit protein degradation, and regulate the interactions between eIF4E and 4E-BP1 or eIF4G in response to feeding. 相似文献
16.
Scot R Kimball Peter A Farrell Leonard S Jefferson 《Journal of applied physiology》2002,93(3):1168-1180
Protein synthesis in skeletal muscle is modulated in response to a variety of stimuli. Two stimuli receiving a great deal of recent attention are increased amino acid availability and exercise. Both of these effectors stimulate protein synthesis in part through activation of translation initiation. However, the full response of translation initiation and protein synthesis to either effector is not observed in the absence of a minimal concentration of insulin. The combination of insulin and either increased amino acid availability or endurance exercise stimulates translation initiation and protein synthesis in part through activation of the ribosomal protein S6 protein kinase S6K1 as well as through enhanced association of eukaryotic initiation factor eIF4G with eIF4E, an event that promotes binding of mRNA to the ribosome. In contrast, insulin in combination with resistance exercise stimulates translation initiation and protein synthesis through enhanced activity of a guanine nucleotide exchange protein referred to as eIF2B. In both cases, the amount of insulin required for the effects is low, and a concentration of the hormone that approximates that observed in fasting animals is sufficient for maximal stimulation. This review summarizes the results of a number of recent studies that have helped to establish our present understanding of the interactions of insulin, amino acids, and exercise in the regulation of protein synthesis in skeletal muscle. 相似文献
17.
Krawiec BJ Frost RA Vary TC Jefferson LS Lang CH 《American journal of physiology. Endocrinology and metabolism》2005,289(6):E969-E980
The hypothesis of the present study was that rats subjected to short-term unilateral hindlimb immobilization would incur skeletal muscle wasting and concomitant alterations in protein synthesis, controllers of translation, and indexes of protein degradation. Rats were unilaterally casted for 1, 3, or 5 days to avoid complications associated with other disuse models. In the casted limb, gastrocnemius wet weight decreased 12% after 3 days and thereafter remained constant. In contrast, the contralateral control leg displayed a steady growth rate over time. The rate of protein synthesis and translational efficiency were unchanged in the immobilized muscle at day 5. The total amount and phosphorylation state of regulators of translational initiation and elongation were unaltered. The mRNA contents of polyubiquitin and the ubiquitin ligases muscle atrophy F-box (MAFbx)/Atrogin-1 and muscle RING finger 1 (MuRF1) were elevated in immobilized muscle at all time points, with peak expression occurring at day 3. Daily injection of the type II glucocorticoid receptor antagonist RU-486 did not prevent decreases in gastrocnemius wet weight nor increases in mRNA for MAFbx/Atrogin-1 and MuRF1. However, in vivo administration of the proteasome inhibitor Velcade prevented 53% of wet weight loss associated with 3 days of immobilization. These data suggest that the loss of skeletal muscle mass in this model of disuse appears to be glucocorticoid independent, can be partially rescued with a potent proteasome inhibitor, and is associated with enhanced mRNA expression of multiple factors that contribute to ubiquitin- proteasome-dependent degradation and are likely to control the remodeling of immobilized skeletal muscle during atrophy. 相似文献
18.
Bell JA Fujita S Volpi E Cadenas JG Rasmussen BB 《American journal of physiology. Endocrinology and metabolism》2005,289(6):E999-1006
Muscle protein synthesis requires energy and amino acids to proceed and can be stimulated by insulin under certain circumstances. We hypothesized that short-term provision of insulin and nutritional energy would stimulate muscle protein synthesis in healthy subjects only if amino acid availability did not decrease. Using stable isotope techniques, we compared the effects on muscle phenylalanine kinetics across the leg of an amino acid-lowering, high-energy (HE, n = 6, 162 +/- 20 kcal/h) hyperglycemic hyperlipidemic hyperinsulinemic clamp with systemic insulin infusion to a low-energy (LE, n = 6, 35 +/- 3 kcal/h, P < 0.05 vs. HE) euglycemic hyperinsulinemic clamp with local insulin infusion in the femoral artery. Basal blood phenylalanine concentrations and phenylalanine net balance, muscle protein breakdown, and synthesis (nmol.min(-1).100 g leg muscle(-1)) were not different between groups. During insulin infusion, femoral insulinemia increased to a similar extent between groups and blood phenylalanine concentration decreased 27 +/- 3% in the HE group but only 9 +/- 2% in the LE group (P < 0.01 HE vs. LE). Phenylalanine net balance increased in both groups, but the change was greater (P < 0.05) in the LE group. Muscle protein breakdown decreased in the HE group (58 +/- 12 to 35 +/- 7 nmol.min(-1).100 g leg muscle(-1)) and did not change in the LE group. Muscle protein synthesis was unchanged in the HE group (39 +/- 6 to 30 +/- 7 nmol.min(-1).100 g leg muscle(-1)) and increased (P < 0.05) in the LE group (41 +/- 9 to 114 +/- 26 nmol.min(-1).100 g leg muscle(-1)). We conclude that amino acid availability is an important factor in the regulation of muscle protein synthesis in response to insulin, as decreased blood amino acid concentrations override the positive effect of insulin on muscle protein synthesis even if excess energy is provided. 相似文献
19.
Takashi Nagasawa Motoni Kadowaki Tadashi Noguchi Hiroshi Naito 《Bioscience, biotechnology, and biochemistry》2013,77(12):3023-3027
Myofibrillar protein degradation was measured by the rate of Nτ-methylhistidine (MeHis) release from the perfused hindquarters in normal and streptozotocin-induced diabetic rats. In diabetic rats, the rate of MeHis release to the perfusate was elevated 2-fold compared with normal rats. The daily excretion of MeHis into urine was also increased 2-fold in the diabetic rats.Insulin in the perfusate did not suppress the release of MeHis from the perfused muscle in normal rats. On the other hand, in diabetic rats, MeHis release was suppressed by insulin. The high concentration of free MeHis in the diabetic muscle was decreased to the normal level with insulin added to the perfusate. These results give further evidence to show that myofibrillar protein degradation is controlled by insulin. 相似文献
20.
K Asplund 《Hormone research》1975,6(1):12-19
Insulin is released into the circulation early during fetal life, but the physiological significance of the hormone in the fetus is still unclear. The present study was undertaken to evaluate the possible effects of insulin on the protein metabolism of skeletal and heart muscle during the perinatal period in the rat. When incubating hemidiaphragm in a bicarbonate buffer, 0.1 U/ml ox insulin failed to enhance the incorporation of leucine-4,5-3H into muscle protein before birth and during the immediate neonatal period. From 3 days of age onwards a stimulatory effect of insulin on protein synthesis was constantly observed. While insulin thus was ineffective in promoting protein synthesis in hemidiaphragms before the third postnatal day, it significantly enhanced the synthesis in heart muscle at an earlier stage of development. Insulin stimulated the uptake of alpha-aminoisobutyric acid-1-14C into the diaphragm muscle during late fetal life as well as through the early neonatal period. The role of insulin in protein metabolism during fetal life may thus be limited to the augmentation of amino acid transport in skeletal and heart muscle and to a stimulatory effect on protein synthesis only in certain tissue(s), e.g. heart muscle. 相似文献