Rapamycin does not improve insulin sensitivity despite elevated mammalian target of rapamycin complex 1 activity in muscles of ob/ob mice

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 295, Issue 5, 2008, Pages

  Miller, Andrew M ^a   Brestoff, Jonathan R ^a   Phelps, Charles B ^a   Berk, E Zachary ^a   Reynolds IV, Thomas H ^a  

^a SKIDMORE COLLEGE   (United States)

Author keywords

Insulin resistance; Signal transduction; Skeletal muscle

Indexed keywords

INSULIN; MAMMALIAN TARGET OF RAPAMYCIN; PROLINE DERIVATIVE; RAPAMYCIN; S6 KINASE; SERINE; THREONINE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; GLUCOSE TOLERANCE; INSULIN RESISTANCE; INSULIN SENSITIVITY; INSULIN TOLERANCE TEST; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; WILD TYPE;

ANIMALS; ANTI-BACTERIAL AGENTS; BLOOD GLUCOSE; BODY WEIGHT; ELECTROPHORESIS, POLYACRYLAMIDE GEL; GLUCOSE TOLERANCE TEST; INSULIN; INSULIN RECEPTOR SUBSTRATE PROTEINS; INSULIN RESISTANCE; MALE; MICE; MICE, OBESE; MUSCLE, SKELETAL; PHOSPHOPROTEINS; PHOSPHORYLATION; PROTO-ONCOGENE PROTEINS C-AKT; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SIROLIMUS; TRANSCRIPTION FACTORS;

EID: 57349116906     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.90428.2008     Document Type: Article

References (39)

1. Alessi DR, Andjelkovic M, Caudwell FB, Cron P, Morrice N, Cohen P, Hemmings BA. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 15: 6541-6551, 1996.
2. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA 101: 12130-12135, 2004.
3. Berg CE, Lavan BE, Rondinone CM. Rapamycin partially prevents insulin resistance induced by chronic insulin treatment. Biochem Biophys Res Commun 293: 1021-1027, 2002.
4. Bodine SC. mTOR signaling and the molecular adaptation to resistance exercise. Med Sci Sports Exerc 38: 1950-1957, 2006.
5. Carlson CJ, White MF, Rondinone CM. Mammalian target of rapamycin regulates IRS1 serine 307 phosphorylation. Biochem Biophys Res Commun 316: 533-559, 2004.
6. Carvalho-Filho MA, Ueno M, Hirabara SM, Seabra AB, Carvalheira JB, de Oliveira MG, Velloso LA, Curi R, Saad MJ. S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt: a novel mechanism of insulin resistance. Diabetes 54: 959-967, 2005.
7. Chiang GG, Abraham RT. Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase. J Biol Chem 280: 25485-25490, 2005.
8. Di Paolo S, Teutonico A, Leogrande D, Capobianco C, Schena PF. Chronic inhibition of mammalian target of rapamycin signaling downregulates insulin receptor substrates 1 and 2 and AKT activation: A crossroad between cancer and diabetes? J Am Soc Nephrol 17: 2236-2244, 2006.
9. Goodyear LJ, Giorgino F, Sherman LA, Carey J, Smith RJ, Dohm GL. Insulin receptor phosphorylation, insulin receptor substrate-1 phosphorylation, and phosphatidylinositol 3-kinase activity are decreased in intact skeletal muscle strips from obese subjects. J Clin Invest 95: 2195-2204, 1995.
10. Ferraninni E, Bevilacqua S, Lanzone L, Bonadonna R, Brandi L, Oleggini M, Boni C, Buzzigoli G, Ciociaro D, Luzi L, Defronzo RA. Metabolic interactions of amino acids and glucose in healthy humans. Diabetes Nutr Metab 3: 175-186, 1988.
11. Haruta T, Uno T, Kawahara J, Takano A, Egawa K, Sharma PM, Olefsky JM, Kobayashi M. A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol Endocrinol 14: 783-794, 2000.
12. Herschkovitz A, Liu YF, Ilan E, Ronen D, Boura-Halfon S, Zick Y. Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by insulin and inducers of insulin resistance. J Biol Chem 282: 18018-18027, 2007.
13. Kerouz NJ, Hörsch D, Pons S, Kahn CR. Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob/ob) mouse. J Clin Invest 100: 3164-3172, 1997.
14. Khamzina L, Veilleux A, Bergeron S, Marette A. Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance. Endocrinology 146: 1473-1481, 2005.
15. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110: 163-175, 2002.
16. Kovacina KS, Park GY, Bae SS, Guzzetta AW, Schaefer E, Birnbaum MJ, Roth RA. Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. J Biol Chem 278: 10189-10194, 2003.
17. Kovacs P, Hanson RL, Lee YH, Yang X, Kobes S, Permana PA, Bogardus C, Baier LJ. The role of insulin receptor substrate-1 gene (IRS1) in type 2 diabetes in Pima Indians. Diabetes 52: 3005-3009, 2003.
18. National Institute of Diabetes, and Digestive and Kidney Diseases. National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, 2005.
19. Navé BT, Ouwens M, Withers DJ, Alessi DR, Shepherd PR. Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation. Biochem J 344: 427-31, 1999.
20. Patti ME, Brambilla E, Luzi L, Landaker EJ, Kahn CR. Bidirectional modulation of insulin action by amino acids. J Clin Invest 101: 1519-1529, 1998.
21. Pederson TM, Kramer DL, Rondinone CM. Serine/threonine phosphorylation of IRS-1 triggers its degradation. Possible regulation by tyrosine phosphorylation. Diabetes 50: 24-31, 2001.
22. Pisters PWT, Restifo NP, Cersosimo E, Brennan MF. The effects of euglycemic hyperinsulinemia and amino acid infusion on regional and whole body glucose disposal in man. Metabolism 40: 59-65, 1991.
23. Pullen N, Thomas G. The modular phosphorylation and activation of p70s6k. FEBS Lett 410: 78-82, 1997.
24. Reynolds TH, Phelps C. Mammalian target of rapamycin impairs insulin's ability to promote protein kinase B phosphorylation in isolated rat skeletal muscle (Abstract). FASEB J 21: 738.4, 2007.
25. Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 25: 903-915, 2007.
26. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101, 2005.
27. Scott PH, Brunn GJ, Kohn AD, Roth RA, Lawrence JC. Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc Natl Acad Sci USA 95: 7772-7777, 1998.
28. Sekulić 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 60: 3504-3513, 2000.
29. Shah OJ, Wang Z, Hunter T. Inappropriate activation of the TSC/Rheb/ mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol 14: 1650-1656, 2004.
30. She P, Van Horn C, Reid T, Hutson SM, Cooney RN, Lynch CJ. Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism. Am J Physiol Endocrinol Metab 293: E1552-E1563, 2007.
31. Sugita H, Fujimoto F, Yasukawa T, Shimizu N, Sugita M, Yasuhara S, Martyn JAJ, Kaneki M. Inducible nitric oxide snythase and NO donor-induced insulin receptor substrate-1 degradation in skeletal muscle cells. J Biol Chem 280: 14203-14211, 2005.
32. Tappy L, Acheson K, Normand S, Schneeberger D, Thélin A, Pachiaudi C, Riou JP, Jéquier E. Effects of infused amino acids on glucose production and utilization in healthy humans. Am J Physiol Endocrinol Metab 262: E826-E833, 1992.
33. Tremblay F, Gagnon A, Veilleux A, Sorisky A, Marette A. Activation of the mammalian target of rapamycin pathway acutely inhibits insulin signaling to Akt and glucose transport in 3T3-L1 and human adipocytes. Endocrinology 146: 1328-1337, 2005.
34. Tremblay F, Marette A. Amino acid and insulin signaling via the mTOR/p70 S6 kinase pathway. A negative feedback mechanism leading to insulin resistance in skeletal muscle cells. J Biol Chem 276: 38052-38060, 2001.
35. Tzatsos A, Kandror KV. Nutrients suppress phosphatidylinositol 3-kinase/ Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol 26: 63-76, 2006.
36. Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431: 200-205, 2004.
37. Vander Haar E, Lee SI, Bandhakavi S, Griffin TJ, Kim DH. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol 9: 316-323, 2007.
38. Wang X, Proud CG. The mTOR pathway in the control of protein synthesis. Physiology 21: 362-369, 2006.
39. Zhande R, Mitchell JJ, Wu J, Sun XJ. Molecular mechanism of insulin-induced degradation of insulin receptor substrate 1. Mol Cell Biol 22: 1016-1026, 2002.