Skip to main content
Top
Published in: BMC Physiology 1/2011

Open Access 01-12-2011 | Research article

The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes

Authors: Petra Gran, David Cameron-Smith

Published in: BMC Physiology | Issue 1/2011

Login to get access

Abstract

Background

The branched-chain amino acid (BCAA) leucine has been identified to be a key regulator of skeletal muscle anabolism. Activation of anabolic signalling occurs via the mammalian target of rapamycin (mTOR) through an undefined mechanism. System A and L solute carriers transport essential amino acids across plasma membranes; however it remains unknown whether an exogenous supply of leucine regulates their gene expression. The aim of the present study was to investigate the effects of acute and chronic leucine stimulation of anabolic signalling and specific amino acid transporters, using cultured primary human skeletal muscle cells.

Results

Human myotubes were treated with leucine, insulin or co-treated with leucine and insulin for 30 min, 3 h or 24 h. Activation of mTOR signalling kinases were examined, together with putative nutrient sensor human vacuolar protein sorting 34 (hVps34) and gene expression of selected amino acid transporters. Phosphorylation of mTOR and p70S6K was transiently increased following leucine exposure, independently to insulin. hVps34 protein expression was also significantly increased. However, genes encoding amino acid transporters were differentially regulated by insulin and not leucine.

Conclusions

mTOR signalling is transiently activated by leucine within human myotubes independently of insulin stimulation. While this occurred in the absence of changes in gene expression of amino acid transporters, protein expression of hVps34 increased.
Appendix
Available only for authorised users
Literature
1.
go back to reference Nelsen CJ, Rickheim DG, Tucker MM, Hansen LK, Albrecht JH: Evidence that cyclin D1 mediates both growth and proliferation downstream of TOR in hepatocytes. J Biol Chem. 2003, 278: 3656-3663. 10.1074/jbc.M209374200.PubMedCrossRef Nelsen CJ, Rickheim DG, Tucker MM, Hansen LK, Albrecht JH: Evidence that cyclin D1 mediates both growth and proliferation downstream of TOR in hepatocytes. J Biol Chem. 2003, 278: 3656-3663. 10.1074/jbc.M209374200.PubMedCrossRef
2.
go back to reference Nelsen CJ, Rickheim DG, Tucker MM, McKenzie TJ, Hansen LK, Pestell RG, Albrecht JH: Amino acids regulate hepatocyte proliferation through modulation of cyclin D1 expression. J Biol Chem. 2003, 278: 25853-25858. 10.1074/jbc.M302360200.PubMedCrossRef Nelsen CJ, Rickheim DG, Tucker MM, McKenzie TJ, Hansen LK, Pestell RG, Albrecht JH: Amino acids regulate hepatocyte proliferation through modulation of cyclin D1 expression. J Biol Chem. 2003, 278: 25853-25858. 10.1074/jbc.M302360200.PubMedCrossRef
4.
go back to reference Fujita S, Dreyer HC, Drummond MJ, Glynn EL, Volpi E, Rasmussen BB: Essential amino acid and carbohydrate ingestion before resistance exercise does not enhance postexercise muscle protein synthesis. J Appl Physiol. 2009, 106: 1730-1739. 10.1152/japplphysiol.90395.2008.PubMedPubMedCentralCrossRef Fujita S, Dreyer HC, Drummond MJ, Glynn EL, Volpi E, Rasmussen BB: Essential amino acid and carbohydrate ingestion before resistance exercise does not enhance postexercise muscle protein synthesis. J Appl Physiol. 2009, 106: 1730-1739. 10.1152/japplphysiol.90395.2008.PubMedPubMedCentralCrossRef
5.
go back to reference Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, Wackerhage H, Taylor PM, Rennie MJ: Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. Faseb J. 2005, 19: 422-424.PubMed Cuthbertson D, Smith K, Babraj J, Leese G, Waddell T, Atherton P, Wackerhage H, Taylor PM, Rennie MJ: Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. Faseb J. 2005, 19: 422-424.PubMed
6.
go back to reference Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K, Rennie MJ: Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr. 2010 Atherton PJ, Etheridge T, Watt PW, Wilkinson D, Selby A, Rankin D, Smith K, Rennie MJ: Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling. Am J Clin Nutr. 2010
7.
go back to reference Greiwe JS, Kwon G, McDaniel ML, Semenkovich CF: Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle. Am J Physiol Endocrinol Metab. 2001, 281: E466-471.PubMed Greiwe JS, Kwon G, McDaniel ML, Semenkovich CF: Leucine and insulin activate p70 S6 kinase through different pathways in human skeletal muscle. Am J Physiol Endocrinol Metab. 2001, 281: E466-471.PubMed
8.
go back to reference Liu Z, Jahn LA, Wei L, Long W, Barrett EJ: Amino acids stimulate translation initiation and protein synthesis through an Akt-independent pathway in human skeletal muscle. J Clin Endocrinol Metab. 2002, 87: 5553-5558. 10.1210/jc.2002-020424.PubMedCrossRef Liu Z, Jahn LA, Wei L, Long W, Barrett EJ: Amino acids stimulate translation initiation and protein synthesis through an Akt-independent pathway in human skeletal muscle. J Clin Endocrinol Metab. 2002, 87: 5553-5558. 10.1210/jc.2002-020424.PubMedCrossRef
9.
go back to reference Kimball SR, Shantz LM, Horetsky RL, Jefferson LS: Leucine Regulates Translation of Specific mRNAs in L6 Myoblasts through mTOR-mediated Changes in Availability of eIF4E and Phosphorylation of Ribosomal Protein S6. J Biol Chem. 1999, 274: 11647-11652. 10.1074/jbc.274.17.11647.PubMedCrossRef Kimball SR, Shantz LM, Horetsky RL, Jefferson LS: Leucine Regulates Translation of Specific mRNAs in L6 Myoblasts through mTOR-mediated Changes in Availability of eIF4E and Phosphorylation of Ribosomal Protein S6. J Biol Chem. 1999, 274: 11647-11652. 10.1074/jbc.274.17.11647.PubMedCrossRef
10.
go back to reference Anthony JC, Anthony TG, Kimball SR, Jefferson LS: Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr. 2001, 131: 856S-860S.PubMed Anthony JC, Anthony TG, Kimball SR, Jefferson LS: Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr. 2001, 131: 856S-860S.PubMed
11.
go back to reference Hara K, Maruki Y, Long X, Yoshino K-i, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K: Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action. Cell. 2002, 110: 177-189. 10.1016/S0092-8674(02)00833-4.PubMedCrossRef Hara K, Maruki Y, Long X, Yoshino K-i, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K: Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action. Cell. 2002, 110: 177-189. 10.1016/S0092-8674(02)00833-4.PubMedCrossRef
12.
go back to reference Avruch J, Belham C, Weng Q, Hara K, Yonezawa K: The p70 S6 kinase integrates nutrient and growth signals to control translational capacity. Prog Mol Subcell Biol. 2001, 26: 115-154.PubMedCrossRef Avruch J, Belham C, Weng Q, Hara K, Yonezawa K: The p70 S6 kinase integrates nutrient and growth signals to control translational capacity. Prog Mol Subcell Biol. 2001, 26: 115-154.PubMedCrossRef
13.
go back to reference Kozak M, Shatkin AJ: Identification of features in 5' terminal fragments from reovirus mRNA which are important for ribosome binding. Cell. 1978, 13: 201-212. 10.1016/0092-8674(78)90150-2.PubMedCrossRef Kozak M, Shatkin AJ: Identification of features in 5' terminal fragments from reovirus mRNA which are important for ribosome binding. Cell. 1978, 13: 201-212. 10.1016/0092-8674(78)90150-2.PubMedCrossRef
14.
go back to reference Atherton PJ, Smith K, Etheridge T, Rankin D, Rennie MJ: Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells. Amino Acids. 2010, 38: 1533-1539. 10.1007/s00726-009-0377-x.PubMedCrossRef Atherton PJ, Smith K, Etheridge T, Rankin D, Rennie MJ: Distinct anabolic signalling responses to amino acids in C2C12 skeletal muscle cells. Amino Acids. 2010, 38: 1533-1539. 10.1007/s00726-009-0377-x.PubMedCrossRef
15.
go back to reference Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB: Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. 2008, 294: E392-400.PubMedPubMedCentralCrossRef Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, Dhanani S, Volpi E, Rasmussen BB: Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab. 2008, 294: E392-400.PubMedPubMedCentralCrossRef
16.
go back to reference Drummond MJ, Rasmussen BB: Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care. 2008, 11: 222-226. 10.1097/MCO.0b013e3282fa17fb.PubMedCrossRef Drummond MJ, Rasmussen BB: Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care. 2008, 11: 222-226. 10.1097/MCO.0b013e3282fa17fb.PubMedCrossRef
17.
go back to reference Deldicque L, Sanchez Canedo C, Horman S, De Potter I, Bertrand L, Hue L, Francaux M: Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells. Amino Acids. 2008, 35: 147-155. 10.1007/s00726-007-0607-z.PubMedCrossRef Deldicque L, Sanchez Canedo C, Horman S, De Potter I, Bertrand L, Hue L, Francaux M: Antagonistic effects of leucine and glutamine on the mTOR pathway in myogenic C2C12 cells. Amino Acids. 2008, 35: 147-155. 10.1007/s00726-007-0607-z.PubMedCrossRef
18.
go back to reference Glynn E, Fry C, Drummond M, Timmerman K, Dhanani S, Volpi E, Rasmussen B: Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. J Nutr. 2010, 140: 1970-1976. 10.3945/jn.110.127647.PubMedPubMedCentralCrossRef Glynn E, Fry C, Drummond M, Timmerman K, Dhanani S, Volpi E, Rasmussen B: Excess leucine intake enhances muscle anabolic signaling but not net protein anabolism in young men and women. J Nutr. 2010, 140: 1970-1976. 10.3945/jn.110.127647.PubMedPubMedCentralCrossRef
19.
go back to reference Ishizuka Y, Kakiya N, Nawa H, Takei N: Leucine induces phosphorylation and activation of p70S6K in cortical neurons via the system L amino acid transporter. J Neurochem. 2008, 106: 934-942. 10.1111/j.1471-4159.2008.05438.x.PubMedCrossRef Ishizuka Y, Kakiya N, Nawa H, Takei N: Leucine induces phosphorylation and activation of p70S6K in cortical neurons via the system L amino acid transporter. J Neurochem. 2008, 106: 934-942. 10.1111/j.1471-4159.2008.05438.x.PubMedCrossRef
20.
go back to reference Kimball SR, Shantz LM, Horetsky RL, Jefferson LS: Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6. J Biol Chem. 1999, 274: 11647-11652. 10.1074/jbc.274.17.11647.PubMedCrossRef Kimball SR, Shantz LM, Horetsky RL, Jefferson LS: Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6. J Biol Chem. 1999, 274: 11647-11652. 10.1074/jbc.274.17.11647.PubMedCrossRef
21.
go back to reference Norton LE, Layman DK, Bunpo P, Anthony TG, Brana DV, Garlick PJ: The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats. J Nutr. 2009, 139: 1103-1109. 10.3945/jn.108.103853.PubMedCrossRef Norton LE, Layman DK, Bunpo P, Anthony TG, Brana DV, Garlick PJ: The leucine content of a complete meal directs peak activation but not duration of skeletal muscle protein synthesis and mammalian target of rapamycin signaling in rats. J Nutr. 2009, 139: 1103-1109. 10.3945/jn.108.103853.PubMedCrossRef
22.
go back to reference Shah OJ, Antonetti DA, Kimball SR, Jefferson LS: Leucine, glutamine, and tyrosine reciprocally modulate the translation initiation factors eIF4F and eIF2B in perfused rat liver. J Biol Chem. 1999, 274: 36168-36175. 10.1074/jbc.274.51.36168.PubMedCrossRef Shah OJ, Antonetti DA, Kimball SR, Jefferson LS: Leucine, glutamine, and tyrosine reciprocally modulate the translation initiation factors eIF4F and eIF2B in perfused rat liver. J Biol Chem. 1999, 274: 36168-36175. 10.1074/jbc.274.51.36168.PubMedCrossRef
23.
go back to reference Iraqui I, Vissers S, Bernard F, de Craene JO, Boles E, Urrestarazu A, Andre B: Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease. Mol Cell Biol. 1999, 19: 989-1001.PubMedPubMedCentralCrossRef Iraqui I, Vissers S, Bernard F, de Craene JO, Boles E, Urrestarazu A, Andre B: Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and F-Box protein Grr1p are required for transcriptional induction of the AGP1 gene, which encodes a broad-specificity amino acid permease. Mol Cell Biol. 1999, 19: 989-1001.PubMedPubMedCentralCrossRef
24.
go back to reference Ferenci T: Regulation by nutrient limitation. Curr Opin Microbiol. 1999, 2: 208-213. 10.1016/S1369-5274(99)80036-8.PubMedCrossRef Ferenci T: Regulation by nutrient limitation. Curr Opin Microbiol. 1999, 2: 208-213. 10.1016/S1369-5274(99)80036-8.PubMedCrossRef
25.
go back to reference Findlay GM, Yan L, Procter J, Mieulet V, Lamb RF: A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007, 403: 13-20. 10.1042/BJ20061881.PubMedPubMedCentralCrossRef Findlay GM, Yan L, Procter J, Mieulet V, Lamb RF: A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling. Biochem J. 2007, 403: 13-20. 10.1042/BJ20061881.PubMedPubMedCentralCrossRef
26.
go back to reference Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM: The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008, 320: 1496-1501. 10.1126/science.1157535.PubMedPubMedCentralCrossRef Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM: The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science. 2008, 320: 1496-1501. 10.1126/science.1157535.PubMedPubMedCentralCrossRef
27.
go back to reference Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer J, Matt F, Bos JL, Zwartkruis FJ, Thomas G: Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci USA. 2005, 102: 14238-14243. 10.1073/pnas.0506925102.PubMedPubMedCentralCrossRef Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer J, Matt F, Bos JL, Zwartkruis FJ, Thomas G: Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci USA. 2005, 102: 14238-14243. 10.1073/pnas.0506925102.PubMedPubMedCentralCrossRef
28.
go back to reference MacKenzie MG, Hamilton DL, Murray JT, Taylor PM, Baar K: mVps34 is activated following high-resistance contractions. J Physiol. 2009, 587: 253-260. 10.1113/jphysiol.2008.159830.PubMedPubMedCentralCrossRef MacKenzie MG, Hamilton DL, Murray JT, Taylor PM, Baar K: mVps34 is activated following high-resistance contractions. J Physiol. 2009, 587: 253-260. 10.1113/jphysiol.2008.159830.PubMedPubMedCentralCrossRef
29.
go back to reference Byfield MP, Murray JT, Backer JM: hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem. 2005, 280: 33076-33082. 10.1074/jbc.M507201200.PubMedCrossRef Byfield MP, Murray JT, Backer JM: hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J Biol Chem. 2005, 280: 33076-33082. 10.1074/jbc.M507201200.PubMedCrossRef
30.
go back to reference Bodoy S, Martin L, Zorzano A, Palacin M, Estevez R, Bertran J: Identification of LAT4, a novel amino acid transporter with system L activity. J Biol Chem. 2005, 280: 12002-12011. 10.1074/jbc.M408638200.PubMedCrossRef Bodoy S, Martin L, Zorzano A, Palacin M, Estevez R, Bertran J: Identification of LAT4, a novel amino acid transporter with system L activity. J Biol Chem. 2005, 280: 12002-12011. 10.1074/jbc.M408638200.PubMedCrossRef
31.
go back to reference Riggs TR, McKirahan KJ: Action of insulin on transport of L-alanine into rat diaphragm in vitro. Evidence that the hormone affects only one neutral amino acid transport system. J Biol Chem. 1973, 248: 6450-6455.PubMed Riggs TR, McKirahan KJ: Action of insulin on transport of L-alanine into rat diaphragm in vitro. Evidence that the hormone affects only one neutral amino acid transport system. J Biol Chem. 1973, 248: 6450-6455.PubMed
32.
go back to reference Zorzano A, Balon TW, Goodman MN, Ruderman NB: Insulin and exercise stimulate muscle alpha-aminoisobutyric acid transport by a Na+-K+-ATPase independent pathway. Biochem Biophys Res Commun. 1986, 134: 1342-1349. 10.1016/0006-291X(86)90397-9.PubMedCrossRef Zorzano A, Balon TW, Goodman MN, Ruderman NB: Insulin and exercise stimulate muscle alpha-aminoisobutyric acid transport by a Na+-K+-ATPase independent pathway. Biochem Biophys Res Commun. 1986, 134: 1342-1349. 10.1016/0006-291X(86)90397-9.PubMedCrossRef
33.
go back to reference Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M: Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2008 Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M: Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2008
34.
go back to reference McDowell HE, Christie GR, Stenhouse G, Hundal HS: Leucine activates system A amino acid transport in L6 rat skeletal muscle cells. Am J Physiol. 1995, 269: C1287-1294.PubMed McDowell HE, Christie GR, Stenhouse G, Hundal HS: Leucine activates system A amino acid transport in L6 rat skeletal muscle cells. Am J Physiol. 1995, 269: C1287-1294.PubMed
35.
go back to reference Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, Cha SH, Matsuo H, Fukushima J, Fukasawa Y, Tani Y, Taketani Y, Uchino H, Kim JY, Inatomi J, Okayasu I, Miyamoto K, Takeda E, Goya T, Endou H: Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001, 1514: 291-302. 10.1016/S0005-2736(01)00384-4.PubMedCrossRef Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, Nii T, Cha SH, Matsuo H, Fukushima J, Fukasawa Y, Tani Y, Taketani Y, Uchino H, Kim JY, Inatomi J, Okayasu I, Miyamoto K, Takeda E, Goya T, Endou H: Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines. Biochim Biophys Acta. 2001, 1514: 291-302. 10.1016/S0005-2736(01)00384-4.PubMedCrossRef
36.
go back to reference Kobayashi K, Ohnishi A, Promsuk J, Shimizu S, Kanai Y, Shiokawa Y, Nagane M: Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery. 2008, 62: 493-503. 10.1227/01.neu.0000316018.51292.19. discussion 503-494PubMedCrossRef Kobayashi K, Ohnishi A, Promsuk J, Shimizu S, Kanai Y, Shiokawa Y, Nagane M: Enhanced tumor growth elicited by L-type amino acid transporter 1 in human malignant glioma cells. Neurosurgery. 2008, 62: 493-503. 10.1227/01.neu.0000316018.51292.19. discussion 503-494PubMedCrossRef
37.
go back to reference Gaster M, Kristensen SR, Beck-Nielsen H, Schroder HD: A cellular model system of differentiated human myotubes. APMIS. 2001, 109: 735-744. 10.1034/j.1600-0463.2001.d01-140.x.PubMedCrossRef Gaster M, Kristensen SR, Beck-Nielsen H, Schroder HD: A cellular model system of differentiated human myotubes. APMIS. 2001, 109: 735-744. 10.1034/j.1600-0463.2001.d01-140.x.PubMedCrossRef
38.
go back to reference Wang X, Campbell LE, Miller CM, Proud CG: Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J. 1998, 334 (Pt 1): 261-267.PubMedPubMedCentralCrossRef Wang X, Campbell LE, Miller CM, Proud CG: Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J. 1998, 334 (Pt 1): 261-267.PubMedPubMedCentralCrossRef
39.
go back to reference Xu G, Kwon G, Marshall CA, Lin TA, Lawrence JC, McDaniel ML: Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic beta-cells. A possible role in protein translation and mitogenic signaling. J Biol Chem. 1998, 273: 28178-28184. 10.1074/jbc.273.43.28178.PubMedCrossRef Xu G, Kwon G, Marshall CA, Lin TA, Lawrence JC, McDaniel ML: Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic beta-cells. A possible role in protein translation and mitogenic signaling. J Biol Chem. 1998, 273: 28178-28184. 10.1074/jbc.273.43.28178.PubMedCrossRef
40.
go back to reference Krause U, Bertrand L, Maisin L, Rosa M, Hue L: Signalling pathways and combinatory effects of insulin and amino acids in isolated rat hepatocytes. Eur J Biochem. 2002, 269: 3742-3750. 10.1046/j.1432-1033.2002.03069.x.PubMedCrossRef Krause U, Bertrand L, Maisin L, Rosa M, Hue L: Signalling pathways and combinatory effects of insulin and amino acids in isolated rat hepatocytes. Eur J Biochem. 2002, 269: 3742-3750. 10.1046/j.1432-1033.2002.03069.x.PubMedCrossRef
41.
go back to reference Patti ME, Brambilla E, Luzi L, Landaker EJ, Kahn CR: Bidirectional modulation of insulin action by amino acids. J Clin Invest. 1998, 101: 1519-1529. 10.1172/JCI1326.PubMedPubMedCentralCrossRef Patti ME, Brambilla E, Luzi L, Landaker EJ, Kahn CR: Bidirectional modulation of insulin action by amino acids. J Clin Invest. 1998, 101: 1519-1529. 10.1172/JCI1326.PubMedPubMedCentralCrossRef
42.
go back to reference Dennis MD, Baum JI, Kimball SR, Jefferson LS: Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids. J Biol Chem. 2011, 286: 8287-8296. 10.1074/jbc.M110.209171.PubMedPubMedCentralCrossRef Dennis MD, Baum JI, Kimball SR, Jefferson LS: Mechanisms involved in the coordinate regulation of mTORC1 by insulin and amino acids. J Biol Chem. 2011, 286: 8287-8296. 10.1074/jbc.M110.209171.PubMedPubMedCentralCrossRef
43.
go back to reference Sekulic A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, Abraham RT: A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 2000, 60: 3504-3513.PubMed Sekulic A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, Abraham RT: A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells. Cancer Res. 2000, 60: 3504-3513.PubMed
44.
go back to reference Bolster DR, Vary TC, Kimball SR, Jefferson LS: Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation. J Nutr. 2004, 134: 1704-1710.PubMed Bolster DR, Vary TC, Kimball SR, Jefferson LS: Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation. J Nutr. 2004, 134: 1704-1710.PubMed
45.
go back to reference Hillier T, Long W, Jahn L, Wei L, Barrett EJ: Physiological hyperinsulinemia stimulates p70(S6k) phosphorylation in human skeletal muscle. J Clin Endocrinol Metab. 2000, 85: 4900-4904. 10.1210/jc.85.12.4900.PubMed Hillier T, Long W, Jahn L, Wei L, Barrett EJ: Physiological hyperinsulinemia stimulates p70(S6k) phosphorylation in human skeletal muscle. J Clin Endocrinol Metab. 2000, 85: 4900-4904. 10.1210/jc.85.12.4900.PubMed
46.
go back to reference Kimball SR, Vary TC, Jefferson LS: Regulation of protein synthesis by insulin. Annu Rev Physiol. 1994, 56: 321-348. 10.1146/annurev.ph.56.030194.001541.PubMedCrossRef Kimball SR, Vary TC, Jefferson LS: Regulation of protein synthesis by insulin. Annu Rev Physiol. 1994, 56: 321-348. 10.1146/annurev.ph.56.030194.001541.PubMedCrossRef
48.
go back to reference Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M: Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2009, 36: 219-230. 10.1007/s00726-008-0050-9.PubMedCrossRef Kashiwagi H, Yamazaki K, Takekuma Y, Ganapathy V, Sugawara M: Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal muscle cells by insulin, osmotic shock and amino acid deprivation. Amino Acids. 2009, 36: 219-230. 10.1007/s00726-008-0050-9.PubMedCrossRef
49.
go back to reference Kletzien RF, Pariza MW, Becker JE, Potter VR, Butcher FR: Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin. J Biol Chem. 1976, 251: 3014-3020.PubMed Kletzien RF, Pariza MW, Becker JE, Potter VR, Butcher FR: Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin. J Biol Chem. 1976, 251: 3014-3020.PubMed
50.
go back to reference Su TZ, Wang M, Syu LJ, Saltiel AR, Oxender DL: Regulation of system A amino acid transport in 3T3-L1 adipocytes by insulin. J Biol Chem. 1998, 273: 3173-3179. 10.1074/jbc.273.6.3173.PubMedCrossRef Su TZ, Wang M, Syu LJ, Saltiel AR, Oxender DL: Regulation of system A amino acid transport in 3T3-L1 adipocytes by insulin. J Biol Chem. 1998, 273: 3173-3179. 10.1074/jbc.273.6.3173.PubMedCrossRef
51.
go back to reference Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H: Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998, 273: 23629-23632. 10.1074/jbc.273.37.23629.PubMedCrossRef Kanai Y, Segawa H, Miyamoto K, Uchino H, Takeda E, Endou H: Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98). J Biol Chem. 1998, 273: 23629-23632. 10.1074/jbc.273.37.23629.PubMedCrossRef
52.
go back to reference Segawa H, Fukasawa Y, Miyamoto K, Takeda E, Endou H, Kanai Y: Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity. J Biol Chem. 1999, 274: 19745-19751. 10.1074/jbc.274.28.19745.PubMedCrossRef Segawa H, Fukasawa Y, Miyamoto K, Takeda E, Endou H, Kanai Y: Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity. J Biol Chem. 1999, 274: 19745-19751. 10.1074/jbc.274.28.19745.PubMedCrossRef
53.
go back to reference Caldow MK, Steinberg GR, Cameron-Smith D: Impact of SOCS3 overexpression on human skeletal muscle development in vitro. Cytokine. In Press, Corrected Proof Caldow MK, Steinberg GR, Cameron-Smith D: Impact of SOCS3 overexpression on human skeletal muscle development in vitro. Cytokine. In Press, Corrected Proof
54.
go back to reference Evans WJ, Phinney SD, Young VR: Suction applied to a muscle biopsy maximizes sample size. Med Sci Sports Exerc. 1982, 14: 101-102.PubMed Evans WJ, Phinney SD, Young VR: Suction applied to a muscle biopsy maximizes sample size. Med Sci Sports Exerc. 1982, 14: 101-102.PubMed
55.
go back to reference Rando TA, Blau HM: Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J Cell Biol. 1994, 125: 1275-1287. 10.1083/jcb.125.6.1275.PubMedCrossRef Rando TA, Blau HM: Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy. J Cell Biol. 1994, 125: 1275-1287. 10.1083/jcb.125.6.1275.PubMedCrossRef
Metadata
Title
The actions of exogenous leucine on mTOR signalling and amino acid transporters in human myotubes
Authors
Petra Gran
David Cameron-Smith
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Physiology / Issue 1/2011
Electronic ISSN: 1472-6793
DOI
https://doi.org/10.1186/1472-6793-11-10

Other articles of this Issue 1/2011

BMC Physiology 1/2011 Go to the issue