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Published in: Cardiovascular Diabetology 1/2012

Open Access 01-12-2012 | Review

Mammalian target of rapamycin signaling in diabetic cardiovascular disease

Authors: Zhao Zhong Chong, Kenneth Maiese

Published in: Cardiovascular Diabetology | Issue 1/2012

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Abstract

Diabetes mellitus currently affects more than 170 million individuals worldwide and is expected to afflict another 200 million individuals in the next 30 years. Complications of diabetes as a result of oxidant stress affect multiple systems throughout the body, but involvement of the cardiovascular system may be one of the most severe in light of the impact upon cardiac and vascular function that can result in rapid morbidity and mortality for individuals. Given these concerns, the signaling pathways of the mammalian target of rapamycin (mTOR) offer exciting prospects for the development of novel therapies for the cardiovascular complications of diabetes. In the cardiovascular and metabolic systems, mTOR and its multi-protein complexes of TORC1 and TORC2 regulate insulin release and signaling, endothelial cell survival and growth, cardiomyocyte proliferation, resistance to β-cell injury, and cell longevity. Yet, mTOR can, at times, alter insulin signaling and lead to insulin resistance in the cardiovascular system during diabetes mellitus. It is therefore vital to understand the complex relationship mTOR and its downstream pathways hold during metabolic disease in order to develop novel strategies for the complications of diabetes mellitus in the cardiovascular system.
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Literature
1.
go back to reference Chong ZZ, Shang YC, Zhang L, Wang S, Maiese K: Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders. Oxid Med Cell Longev. 2010, 3: 374-391. 10.4161/oxim.3.6.14787.PubMedCentralPubMed Chong ZZ, Shang YC, Zhang L, Wang S, Maiese K: Mammalian target of rapamycin: hitting the bull's-eye for neurological disorders. Oxid Med Cell Longev. 2010, 3: 374-391. 10.4161/oxim.3.6.14787.PubMedCentralPubMed
2.
go back to reference Heitman J, Movva NR, Hall MN: Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science. 1991, 253: 905-909. 10.1126/science.1715094.PubMed Heitman J, Movva NR, Hall MN: Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science. 1991, 253: 905-909. 10.1126/science.1715094.PubMed
4.
go back to reference Hwang SK, Kim HH: The functions of mTOR in ischemic diseases. BMB Rep. 2011, 44: 506-511. 10.5483/BMBRep.2011.44.8.506.PubMed Hwang SK, Kim HH: The functions of mTOR in ischemic diseases. BMB Rep. 2011, 44: 506-511. 10.5483/BMBRep.2011.44.8.506.PubMed
5.
go back to reference Abraham RT: mTOR as a positive regulator of tumor cell responses to hypoxia. Curr Top Microbiol Immunol. 2004, 279: 299-319. 10.1007/978-3-642-18930-2_18.PubMed Abraham RT: mTOR as a positive regulator of tumor cell responses to hypoxia. Curr Top Microbiol Immunol. 2004, 279: 299-319. 10.1007/978-3-642-18930-2_18.PubMed
6.
go back to reference Ekim B, Magnuson B, Acosta-Jaquez HA, Keller JA, Feener EP, Fingar DC: mTOR Kinase Domain Phosphorylation Promotes mTORC1 Signaling, Cell Growth, and Cell Cycle Progression. Mol Cell Biol. 2011, 31: 2787-2801. 10.1128/MCB.05437-11.PubMedCentralPubMed Ekim B, Magnuson B, Acosta-Jaquez HA, Keller JA, Feener EP, Fingar DC: mTOR Kinase Domain Phosphorylation Promotes mTORC1 Signaling, Cell Growth, and Cell Cycle Progression. Mol Cell Biol. 2011, 31: 2787-2801. 10.1128/MCB.05437-11.PubMedCentralPubMed
7.
go back to reference Soliman GA, Acosta-Jaquez HA, Dunlop EA, Ekim B, Maj NE, Tee AR, Fingar DC: mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action. J Biol Chem. 2010, 285: 7866-7879. 10.1074/jbc.M109.096222.PubMedCentralPubMed Soliman GA, Acosta-Jaquez HA, Dunlop EA, Ekim B, Maj NE, Tee AR, Fingar DC: mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action. J Biol Chem. 2010, 285: 7866-7879. 10.1074/jbc.M109.096222.PubMedCentralPubMed
8.
go back to reference Reynolds THt, Bodine SC, Lawrence JC: Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem. 2002, 277: 17657-17662. 10.1074/jbc.M201142200.PubMed Reynolds THt, Bodine SC, Lawrence JC: Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. J Biol Chem. 2002, 277: 17657-17662. 10.1074/jbc.M201142200.PubMed
9.
go back to reference 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 U S A. 1998, 95: 7772-7777. 10.1073/pnas.95.13.7772.PubMedCentralPubMed 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 U S A. 1998, 95: 7772-7777. 10.1073/pnas.95.13.7772.PubMedCentralPubMed
10.
go back to reference Takahashi T, Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K: Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro. Genes Cells. 2000, 5: 765-775. 10.1046/j.1365-2443.2000.00365.x.PubMed Takahashi T, Hara K, Inoue H, Kawa Y, Tokunaga C, Hidayat S, Yoshino K, Kuroda Y, Yonezawa K: Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and in vitro. Genes Cells. 2000, 5: 765-775. 10.1046/j.1365-2443.2000.00365.x.PubMed
11.
go back to reference Chen J, Zheng XF, Brown EJ, Schreiber SL: Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue. Proc Natl Acad Sci U S A. 1995, 92: 4947-4951. 10.1073/pnas.92.11.4947.PubMedCentralPubMed Chen J, Zheng XF, Brown EJ, Schreiber SL: Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue. Proc Natl Acad Sci U S A. 1995, 92: 4947-4951. 10.1073/pnas.92.11.4947.PubMedCentralPubMed
12.
go back to reference Takahara T, Hara K, Yonezawa K, Sorimachi H, Maeda T: Nutrient-dependent multimerization of the mammalian target of rapamycin through the N-terminal HEAT repeat region. J Biol Chem. 2006, 281: 28605-28614. 10.1074/jbc.M606087200.PubMed Takahara T, Hara K, Yonezawa K, Sorimachi H, Maeda T: Nutrient-dependent multimerization of the mammalian target of rapamycin through the N-terminal HEAT repeat region. J Biol Chem. 2006, 281: 28605-28614. 10.1074/jbc.M606087200.PubMed
13.
go back to reference Acosta-Jaquez HA, Keller JA, Foster KG, Ekim B, Soliman GA, Feener EP, Ballif BA, Fingar DC: Site-specific mTOR phosphorylation promotes mTORC1-mediated signaling and cell growth. Mol Cell Biol. 2009, 29: 4308-4324. 10.1128/MCB.01665-08.PubMedCentralPubMed Acosta-Jaquez HA, Keller JA, Foster KG, Ekim B, Soliman GA, Feener EP, Ballif BA, Fingar DC: Site-specific mTOR phosphorylation promotes mTORC1-mediated signaling and cell growth. Mol Cell Biol. 2009, 29: 4308-4324. 10.1128/MCB.01665-08.PubMedCentralPubMed
14.
go back to reference Martin DE, Hall MN: The expanding TOR signaling network. Curr Opin Cell Biol. 2005, 17: 158-166. 10.1016/j.ceb.2005.02.008.PubMed Martin DE, Hall MN: The expanding TOR signaling network. Curr Opin Cell Biol. 2005, 17: 158-166. 10.1016/j.ceb.2005.02.008.PubMed
15.
go back to reference 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. 2002, 110: 163-175. 10.1016/S0092-8674(02)00808-5.PubMed 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. 2002, 110: 163-175. 10.1016/S0092-8674(02)00808-5.PubMed
16.
go back to reference Benjamin D, Colombi M, Moroni C, Hall MN: Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov. 2011, 10: 868-880. 10.1038/nrd3531.PubMed Benjamin D, Colombi M, Moroni C, Hall MN: Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov. 2011, 10: 868-880. 10.1038/nrd3531.PubMed
17.
go back to reference Wang H, Zhang Q, Wen Q, Zheng Y, Philip L, Jiang H, Lin J, Zheng W: Proline-rich Akt substrate of 40 kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway. Cell Signal. 2012, 24: 17-24. 10.1016/j.cellsig.2011.08.010.PubMed Wang H, Zhang Q, Wen Q, Zheng Y, Philip L, Jiang H, Lin J, Zheng W: Proline-rich Akt substrate of 40 kDa (PRAS40): a novel downstream target of PI3k/Akt signaling pathway. Cell Signal. 2012, 24: 17-24. 10.1016/j.cellsig.2011.08.010.PubMed
18.
go back to reference Wang L, Harris TE, Roth RA, Lawrence JC: PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem. 2007, 282: 20036-20044. 10.1074/jbc.M702376200.PubMed Wang L, Harris TE, Roth RA, Lawrence JC: PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding. J Biol Chem. 2007, 282: 20036-20044. 10.1074/jbc.M702376200.PubMed
19.
go back to reference 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. 2007, 25: 903-915. 10.1016/j.molcel.2007.03.003.PubMed 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. 2007, 25: 903-915. 10.1016/j.molcel.2007.03.003.PubMed
20.
go back to reference Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM: Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006, 11: 859-871. 10.1016/j.devcel.2006.10.007.PubMed Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM: Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006, 11: 859-871. 10.1016/j.devcel.2006.10.007.PubMed
21.
go back to reference Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS: Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012, 335: 1638-1643. 10.1126/science.1215135.PubMedCentralPubMed Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS: Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012, 335: 1638-1643. 10.1126/science.1215135.PubMedCentralPubMed
22.
go back to reference Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM: DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009, 137: 873-886. 10.1016/j.cell.2009.03.046.PubMedCentralPubMed Peterson TR, Laplante M, Thoreen CC, Sancak Y, Kang SA, Kuehl WM, Gray NS, Sabatini DM: DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival. Cell. 2009, 137: 873-886. 10.1016/j.cell.2009.03.046.PubMedCentralPubMed
23.
go back to reference Hara K, Maruki Y, Long X, Yoshino K, 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.PubMed Hara K, Maruki Y, Long X, Yoshino K, 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.PubMed
24.
go back to reference Jastrzebski K, Hannan KM, Tchoubrieva EB, Hannan RD, Pearson RB: Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function. Growth Factors. 2007, 25: 209-226. 10.1080/08977190701779101.PubMed Jastrzebski K, Hannan KM, Tchoubrieva EB, Hannan RD, Pearson RB: Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function. Growth Factors. 2007, 25: 209-226. 10.1080/08977190701779101.PubMed
25.
go back to reference Bhandari BK, Feliers D, Duraisamy S, Stewart JL, Gingras AC, Abboud HE, Choudhury GG, Sonenberg N, Kasinath BS: Insulin regulation of protein translation repressor 4E-BP1, an eIF4E-binding protein, in renal epithelial cells. Kidney Int. 2001, 59: 866-875. 10.1046/j.1523-1755.2001.059003866.x.PubMed Bhandari BK, Feliers D, Duraisamy S, Stewart JL, Gingras AC, Abboud HE, Choudhury GG, Sonenberg N, Kasinath BS: Insulin regulation of protein translation repressor 4E-BP1, an eIF4E-binding protein, in renal epithelial cells. Kidney Int. 2001, 59: 866-875. 10.1046/j.1523-1755.2001.059003866.x.PubMed
26.
go back to reference Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN: Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol. 2004, 6: 1122-1128. 10.1038/ncb1183.PubMed Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN: Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol. 2004, 6: 1122-1128. 10.1038/ncb1183.PubMed
27.
go back to reference Rosner M, Fuchs C, Siegel N, Valli A, Hengstschlager M: Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle. Hum Mol Genet. 2009, 18: 3298-3310. 10.1093/hmg/ddp271.PubMedCentralPubMed Rosner M, Fuchs C, Siegel N, Valli A, Hengstschlager M: Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle. Hum Mol Genet. 2009, 18: 3298-3310. 10.1093/hmg/ddp271.PubMedCentralPubMed
28.
go back to reference Dada S, Demartines N, Dormond O: mTORC2 regulates PGE2-mediated endothelial cell survival and migration. Biochem Biophys Res Commun. 2008, 372: 875-879. 10.1016/j.bbrc.2008.05.154.PubMed Dada S, Demartines N, Dormond O: mTORC2 regulates PGE2-mediated endothelial cell survival and migration. Biochem Biophys Res Commun. 2008, 372: 875-879. 10.1016/j.bbrc.2008.05.154.PubMed
29.
go back to reference Kumar A, Harris TE, Keller SR, Choi KM, Magnuson MA, Lawrence JC: Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances Basal glycogen synthase activity. Mol Cell Biol. 2008, 28: 61-70. 10.1128/MCB.01405-07.PubMedCentralPubMed Kumar A, Harris TE, Keller SR, Choi KM, Magnuson MA, Lawrence JC: Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances Basal glycogen synthase activity. Mol Cell Biol. 2008, 28: 61-70. 10.1128/MCB.01405-07.PubMedCentralPubMed
30.
go back to reference Sarbassov DD, Guertin DA, Ali SM, Sabatini DM: Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005, 307: 1098-1101. 10.1126/science.1106148.PubMed Sarbassov DD, Guertin DA, Ali SM, Sabatini DM: Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005, 307: 1098-1101. 10.1126/science.1106148.PubMed
31.
go back to reference Frias MA, Thoreen CC, Jaffe JD, Schroder W, Sculley T, Carr SA, Sabatini DM: mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol. 2006, 16: 1865-1870. 10.1016/j.cub.2006.08.001.PubMed Frias MA, Thoreen CC, Jaffe JD, Schroder W, Sculley T, Carr SA, Sabatini DM: mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr Biol. 2006, 16: 1865-1870. 10.1016/j.cub.2006.08.001.PubMed
32.
go back to reference Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B: SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell. 2006, 127: 125-137. 10.1016/j.cell.2006.08.033.PubMed Jacinto E, Facchinetti V, Liu D, Soto N, Wei S, Jung SY, Huang Q, Qin J, Su B: SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell. 2006, 127: 125-137. 10.1016/j.cell.2006.08.033.PubMed
33.
go back to reference Chen CH, Sarbassov DD: The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2. J Biol Chem. 2011, 286: 40386-40394. 10.1074/jbc.M111.282590.PubMedCentralPubMed Chen CH, Sarbassov DD: The mTOR (mammalian target of rapamycin) kinase maintains integrity of mTOR complex 2. J Biol Chem. 2011, 286: 40386-40394. 10.1074/jbc.M111.282590.PubMedCentralPubMed
34.
go back to reference Pearce LR, Huang X, Boudeau J, Pawlowski R, Wullschleger S, Deak M, Ibrahim AF, Gourlay R, Magnuson MA, Alessi DR: Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J. 2007, 405: 513-522. 10.1042/BJ20070540.PubMedCentralPubMed Pearce LR, Huang X, Boudeau J, Pawlowski R, Wullschleger S, Deak M, Ibrahim AF, Gourlay R, Magnuson MA, Alessi DR: Identification of Protor as a novel Rictor-binding component of mTOR complex-2. Biochem J. 2007, 405: 513-522. 10.1042/BJ20070540.PubMedCentralPubMed
35.
go back to reference Pearce LR, Sommer EM, Sakamoto K, Wullschleger S, Alessi DR: Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney. Biochem J. 2011, 436: 169-179. 10.1042/BJ20102103.PubMed Pearce LR, Sommer EM, Sakamoto K, Wullschleger S, Alessi DR: Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney. Biochem J. 2011, 436: 169-179. 10.1042/BJ20102103.PubMed
36.
go back to reference Hernandez-Negrete I, Carretero-Ortega J, Rosenfeldt H, Hernandez-Garcia R, Calderon-Salinas JV, Reyes-Cruz G, Gutkind JS, Vazquez-Prado J: P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. J Biol Chem. 2007, 282: 23708-23715. 10.1074/jbc.M703771200.PubMed Hernandez-Negrete I, Carretero-Ortega J, Rosenfeldt H, Hernandez-Garcia R, Calderon-Salinas JV, Reyes-Cruz G, Gutkind JS, Vazquez-Prado J: P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. J Biol Chem. 2007, 282: 23708-23715. 10.1074/jbc.M703771200.PubMed
37.
go back to reference Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM: Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004, 14: 1296-1302. 10.1016/j.cub.2004.06.054.PubMed Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM: Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004, 14: 1296-1302. 10.1016/j.cub.2004.06.054.PubMed
38.
go back to reference Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, Lee EY, Weiss HL, O'Connor KL, Gao T, Evers BM: mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res. 2011, 71: 3246-3256. 10.1158/0008-5472.CAN-10-4058.PubMedCentralPubMed Gulhati P, Bowen KA, Liu J, Stevens PD, Rychahou PG, Chen M, Lee EY, Weiss HL, O'Connor KL, Gao T, Evers BM: mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. Cancer Res. 2011, 71: 3246-3256. 10.1158/0008-5472.CAN-10-4058.PubMedCentralPubMed
39.
go back to reference Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB: Diabetes in Asia: epidemiology, risk factors, and pathophysiology. Jama. 2009, 301: 2129-2140. 10.1001/jama.2009.726.PubMed Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB: Diabetes in Asia: epidemiology, risk factors, and pathophysiology. Jama. 2009, 301: 2129-2140. 10.1001/jama.2009.726.PubMed
40.
go back to reference Maiese K, Chong ZZ, Shang YC: Mechanistic insights into diabetes mellitus and oxidative stress. Curr Med Chem. 2007, 14: 1729-1738.PubMedCentralPubMed Maiese K, Chong ZZ, Shang YC: Mechanistic insights into diabetes mellitus and oxidative stress. Curr Med Chem. 2007, 14: 1729-1738.PubMedCentralPubMed
41.
go back to reference Maiese K, Shang YC, Chong ZZ, Hou J: Diabetes mellitus: channeling care through cellular discovery. Curr Neurovasc Res. 2010, 7: 59-64. 10.2174/156720210790820217.PubMedCentralPubMed Maiese K, Shang YC, Chong ZZ, Hou J: Diabetes mellitus: channeling care through cellular discovery. Curr Neurovasc Res. 2010, 7: 59-64. 10.2174/156720210790820217.PubMedCentralPubMed
42.
go back to reference Melnik BC, John SM, Schmitz G: Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome. Nutr Metab (Lond). 2011, 8: 41-10.1186/1743-7075-8-41. Melnik BC, John SM, Schmitz G: Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome. Nutr Metab (Lond). 2011, 8: 41-10.1186/1743-7075-8-41.
43.
go back to reference Harris MI, Eastman RC: Early detection of undiagnosed diabetes mellitus: a US perspective. Diabetes Metab Res Rev. 2000, 16: 230-236. 10.1002/1520-7560(2000)9999:9999<::AID-DMRR122>3.0.CO;2-W.PubMed Harris MI, Eastman RC: Early detection of undiagnosed diabetes mellitus: a US perspective. Diabetes Metab Res Rev. 2000, 16: 230-236. 10.1002/1520-7560(2000)9999:9999<::AID-DMRR122>3.0.CO;2-W.PubMed
44.
go back to reference Kurban S, Mehmetoglu I, Yerlikaya HF, Gonen S, Erdem S: Effect of chronic regular exercise on serum ischemia-modified albumin levels and oxidative stress in type 2 diabetes mellitus. Endocr Res. 2011, 36: 116-123. 10.3109/07435800.2011.566236.PubMed Kurban S, Mehmetoglu I, Yerlikaya HF, Gonen S, Erdem S: Effect of chronic regular exercise on serum ischemia-modified albumin levels and oxidative stress in type 2 diabetes mellitus. Endocr Res. 2011, 36: 116-123. 10.3109/07435800.2011.566236.PubMed
45.
go back to reference Yang H, Jin X, Kei Lam CW, Yan SK: Oxidative stress and diabetes mellitus. Clin Chem Lab Med. 2011, 49: 1773-1782.PubMed Yang H, Jin X, Kei Lam CW, Yan SK: Oxidative stress and diabetes mellitus. Clin Chem Lab Med. 2011, 49: 1773-1782.PubMed
46.
go back to reference Daneman D: Type 1 diabetes. Lancet. 2006, 367: 847-858. 10.1016/S0140-6736(06)68341-4.PubMed Daneman D: Type 1 diabetes. Lancet. 2006, 367: 847-858. 10.1016/S0140-6736(06)68341-4.PubMed
47.
go back to reference Maiese K, Chong ZZ, Shang YC, Hou J: Novel Avenues of Drug Discovery and Biomarkers for Diabetes Mellitus. J Clin Pharmacol. 2011, 51: 128-152. 10.1177/0091270010362904.PubMedCentralPubMed Maiese K, Chong ZZ, Shang YC, Hou J: Novel Avenues of Drug Discovery and Biomarkers for Diabetes Mellitus. J Clin Pharmacol. 2011, 51: 128-152. 10.1177/0091270010362904.PubMedCentralPubMed
48.
go back to reference Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI: Insulin resistance and risk for stroke. Neurology. 2002, 59: 809-815. 10.1212/WNL.59.6.809.PubMed Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI: Insulin resistance and risk for stroke. Neurology. 2002, 59: 809-815. 10.1212/WNL.59.6.809.PubMed
49.
go back to reference Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY, Smithline Kinder L, Ellis D, Becker DJ: Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care. 2003, 26: 1374-1379. 10.2337/diacare.26.5.1374.PubMed Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY, Smithline Kinder L, Ellis D, Becker DJ: Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care. 2003, 26: 1374-1379. 10.2337/diacare.26.5.1374.PubMed
50.
go back to reference Maiese K, Chong ZZ, Shang YC, Hou J: FoxO proteins: cunning concepts and considerations for the cardiovascular system. Clin Sci (Lond). 2009, 116: 191-203. 10.1042/CS20080113. Maiese K, Chong ZZ, Shang YC, Hou J: FoxO proteins: cunning concepts and considerations for the cardiovascular system. Clin Sci (Lond). 2009, 116: 191-203. 10.1042/CS20080113.
51.
go back to reference Reagan LP: Diabetes as a chronic metabolic stressor: causes, consequences and clinical complications. Exp Neurol. 2012, 233: 68-78. 10.1016/j.expneurol.2011.02.004.PubMedCentralPubMed Reagan LP: Diabetes as a chronic metabolic stressor: causes, consequences and clinical complications. Exp Neurol. 2012, 233: 68-78. 10.1016/j.expneurol.2011.02.004.PubMedCentralPubMed
52.
go back to reference Donath MY, Ehses JA, Maedler K, Schumann DM, Ellingsgaard H, Eppler E, Reinecke M: Mechanisms of beta-cell death in type 2 diabetes. Diabetes. 2005, 54 (Suppl 2): S108-113.PubMed Donath MY, Ehses JA, Maedler K, Schumann DM, Ellingsgaard H, Eppler E, Reinecke M: Mechanisms of beta-cell death in type 2 diabetes. Diabetes. 2005, 54 (Suppl 2): S108-113.PubMed
53.
go back to reference Maiese K, Hou J, Chong ZZ, Shang YC: Erythropoietin, forkhead proteins, and oxidative injury: biomarkers and biology. ScientificWorldJournal. 2009, 9: 1072-1104.PubMedCentralPubMed Maiese K, Hou J, Chong ZZ, Shang YC: Erythropoietin, forkhead proteins, and oxidative injury: biomarkers and biology. ScientificWorldJournal. 2009, 9: 1072-1104.PubMedCentralPubMed
54.
go back to reference Zengi A, Ercan G, Caglayan O, Tamsel S, Karadeniz M, Simsir I, Harman E, Kahraman C, Orman M, Cetinkalp S, Ozgen G: Increased oxidative DNA damage in lean normoglycemic offspring of type 2 diabetic patients. Exp Clin Endocrinol Diabetes. 2011, 119: 467-471. 10.1055/s-0031-1275289.PubMed Zengi A, Ercan G, Caglayan O, Tamsel S, Karadeniz M, Simsir I, Harman E, Kahraman C, Orman M, Cetinkalp S, Ozgen G: Increased oxidative DNA damage in lean normoglycemic offspring of type 2 diabetic patients. Exp Clin Endocrinol Diabetes. 2011, 119: 467-471. 10.1055/s-0031-1275289.PubMed
55.
go back to reference Afanas'ev I: Signaling of reactive oxygen and nitrogen species in Diabetes mellitus. Oxid Med Cell Longev. 2010, 3: 361-373. 10.4161/oxim.3.6.14415.PubMedCentralPubMed Afanas'ev I: Signaling of reactive oxygen and nitrogen species in Diabetes mellitus. Oxid Med Cell Longev. 2010, 3: 361-373. 10.4161/oxim.3.6.14415.PubMedCentralPubMed
56.
go back to reference Maiese K, Li F, Chong ZZ: New avenues of exploration for erythropoietin. Jama. 2005, 293: 90-95. 10.1001/jama.293.1.90.PubMedCentralPubMed Maiese K, Li F, Chong ZZ: New avenues of exploration for erythropoietin. Jama. 2005, 293: 90-95. 10.1001/jama.293.1.90.PubMedCentralPubMed
57.
go back to reference Chong ZZ, Shang YC, Maiese K: Vascular injury during elevated glucose can be mitigated by erythropoietin and Wnt signaling. Curr Neurovasc Res. 2007, 4: 194-204.PubMedCentralPubMed Chong ZZ, Shang YC, Maiese K: Vascular injury during elevated glucose can be mitigated by erythropoietin and Wnt signaling. Curr Neurovasc Res. 2007, 4: 194-204.PubMedCentralPubMed
58.
go back to reference Gaddini L, Villa M, Matteucci A, Mallozzi C, Petrucci TC, Di Stasi AM, Leo L, Malchiodi-Albedi F, Pricci F: Early effects of high glucose in retinal tissue cultures Renin-Angiotensin system-dependent and -independent signaling. Neurobiol Dis. 2009, 35: 278-285. 10.1016/j.nbd.2009.05.013.PubMed Gaddini L, Villa M, Matteucci A, Mallozzi C, Petrucci TC, Di Stasi AM, Leo L, Malchiodi-Albedi F, Pricci F: Early effects of high glucose in retinal tissue cultures Renin-Angiotensin system-dependent and -independent signaling. Neurobiol Dis. 2009, 35: 278-285. 10.1016/j.nbd.2009.05.013.PubMed
59.
go back to reference Hou J, Chong ZZ, Shang YC, Maiese K: FoxO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling. Mol Cell Endocrinol. 2010, 321: 194-206. 10.1016/j.mce.2010.02.037.PubMedCentralPubMed Hou J, Chong ZZ, Shang YC, Maiese K: FoxO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling. Mol Cell Endocrinol. 2010, 321: 194-206. 10.1016/j.mce.2010.02.037.PubMedCentralPubMed
60.
go back to reference Gossai D, Lau-Cam CA: The effects of taurine, taurine homologs and hypotaurine on cell and membrane antioxidative system alterations caused by type 2 diabetes in rat erythrocytes. Adv Exp Med Biol. 2009, 643: 359-368. 10.1007/978-0-387-75681-3_37.PubMed Gossai D, Lau-Cam CA: The effects of taurine, taurine homologs and hypotaurine on cell and membrane antioxidative system alterations caused by type 2 diabetes in rat erythrocytes. Adv Exp Med Biol. 2009, 643: 359-368. 10.1007/978-0-387-75681-3_37.PubMed
61.
go back to reference Singh DK, Winocour P, Farrington K: Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol. 2008, 4: 216-226. 10.1038/ncpneph0757.PubMed Singh DK, Winocour P, Farrington K: Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol. 2008, 4: 216-226. 10.1038/ncpneph0757.PubMed
62.
go back to reference Barbosa NB, Oliveira C, Araldi D, Folmer V, Rocha JB, Nogueira CW: Acute diphenyl diselenide treatment reduces hyperglycemia but does not change delta-aminolevulinate dehydratase activity in alloxan-induced diabetes in rats. Biol Pharm Bull. 2008, 31: 2200-2204. 10.1248/bpb.31.2200.PubMed Barbosa NB, Oliveira C, Araldi D, Folmer V, Rocha JB, Nogueira CW: Acute diphenyl diselenide treatment reduces hyperglycemia but does not change delta-aminolevulinate dehydratase activity in alloxan-induced diabetes in rats. Biol Pharm Bull. 2008, 31: 2200-2204. 10.1248/bpb.31.2200.PubMed
63.
go back to reference Maiese K, Chong ZZ, Shang YC: OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins. Trends Mol Med. 2008, 14: 219-227. 10.1016/j.molmed.2008.03.002.PubMedCentralPubMed Maiese K, Chong ZZ, Shang YC: OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins. Trends Mol Med. 2008, 14: 219-227. 10.1016/j.molmed.2008.03.002.PubMedCentralPubMed
64.
go back to reference Chong ZZ, Hou J, Shang YC, Wang S, Maiese K: EPO Relies upon Novel Signaling of Wnt1 that Requires Akt1, FoxO3a, GSK-3beta, and beta-Catenin to Foster Vascular Integrity During Experimental Diabetes. Curr Neurovasc Res. 2011, 8: 103-120. 10.2174/156720211795495402.PubMedCentralPubMed Chong ZZ, Hou J, Shang YC, Wang S, Maiese K: EPO Relies upon Novel Signaling of Wnt1 that Requires Akt1, FoxO3a, GSK-3beta, and beta-Catenin to Foster Vascular Integrity During Experimental Diabetes. Curr Neurovasc Res. 2011, 8: 103-120. 10.2174/156720211795495402.PubMedCentralPubMed
65.
go back to reference Hou J, Chong ZZ, Shang YC, Maiese K: Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation. Curr Neurovasc Res. 2010, 7: 95-112. 10.2174/156720210791184899.PubMedCentralPubMed Hou J, Chong ZZ, Shang YC, Maiese K: Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation. Curr Neurovasc Res. 2010, 7: 95-112. 10.2174/156720210791184899.PubMedCentralPubMed
66.
go back to reference Szabo C: Role of nitrosative stress in the pathogenesis of diabetic vascular dysfunction. Br J Pharmacol. 2009, 156: 713-727. 10.1111/j.1476-5381.2008.00086.x.PubMedCentralPubMed Szabo C: Role of nitrosative stress in the pathogenesis of diabetic vascular dysfunction. Br J Pharmacol. 2009, 156: 713-727. 10.1111/j.1476-5381.2008.00086.x.PubMedCentralPubMed
67.
go back to reference Ceriello A, dello Russo P, Amstad P, Cerutti P: High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. Diabetes. 1996, 45: 471-477. 10.2337/diabetes.45.4.471.PubMed Ceriello A, dello Russo P, Amstad P, Cerutti P: High glucose induces antioxidant enzymes in human endothelial cells in culture. Evidence linking hyperglycemia and oxidative stress. Diabetes. 1996, 45: 471-477. 10.2337/diabetes.45.4.471.PubMed
68.
go back to reference Valle I, Alvarez-Barrientos A, Arza E, Lamas S, Monsalve M: PGC-1alpha regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res. 2005, 66: 562-573. 10.1016/j.cardiores.2005.01.026.PubMed Valle I, Alvarez-Barrientos A, Arza E, Lamas S, Monsalve M: PGC-1alpha regulates the mitochondrial antioxidant defense system in vascular endothelial cells. Cardiovasc Res. 2005, 66: 562-573. 10.1016/j.cardiores.2005.01.026.PubMed
69.
go back to reference Chong ZZ, Kang JQ, Maiese K: Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002, 106: 2973-2979. 10.1161/01.CIR.0000039103.58920.1F.PubMed Chong ZZ, Kang JQ, Maiese K: Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation. 2002, 106: 2973-2979. 10.1161/01.CIR.0000039103.58920.1F.PubMed
70.
go back to reference Li Y, Wu H, Khardori R, Song YH, Lu YW, Geng YJ: Insulin-like growth factor-1 receptor activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. Biochem Biophys Res Commun. 2009, 384: 259-264. 10.1016/j.bbrc.2009.04.113.PubMed Li Y, Wu H, Khardori R, Song YH, Lu YW, Geng YJ: Insulin-like growth factor-1 receptor activation prevents high glucose-induced mitochondrial dysfunction, cytochrome-c release and apoptosis. Biochem Biophys Res Commun. 2009, 384: 259-264. 10.1016/j.bbrc.2009.04.113.PubMed
71.
go back to reference Alexandru N, Popov D, Georgescu A: Platelet dysfunction in vascular pathologies and how can it be treated. Thromb Res. 2012, 129: 116-126. 10.1016/j.thromres.2011.09.026.PubMed Alexandru N, Popov D, Georgescu A: Platelet dysfunction in vascular pathologies and how can it be treated. Thromb Res. 2012, 129: 116-126. 10.1016/j.thromres.2011.09.026.PubMed
72.
go back to reference Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, Antman EM: Diabetes and mortality following acute coronary syndromes. JAMA. 2007, 298: 765-775. 10.1001/jama.298.7.765.PubMed Donahoe SM, Stewart GC, McCabe CH, Mohanavelu S, Murphy SA, Cannon CP, Antman EM: Diabetes and mortality following acute coronary syndromes. JAMA. 2007, 298: 765-775. 10.1001/jama.298.7.765.PubMed
73.
go back to reference Thackeray JT, Radziuk J, Harper ME, Suuronen EJ, Ascah KJ, Beanlands RS, Dasilva JN: Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia. Cardiovasc Diabetol. 2011, 10: 75-10.1186/1475-2840-10-75.PubMedCentralPubMed Thackeray JT, Radziuk J, Harper ME, Suuronen EJ, Ascah KJ, Beanlands RS, Dasilva JN: Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia. Cardiovasc Diabetol. 2011, 10: 75-10.1186/1475-2840-10-75.PubMedCentralPubMed
74.
go back to reference Maiese K, Chong ZZ, Hou J, Shang YC: The vitamin nicotinamide: translating nutrition into clinical care. Molecules. 2009, 14: 3446-3485. 10.3390/molecules14093446.PubMedCentralPubMed Maiese K, Chong ZZ, Hou J, Shang YC: The vitamin nicotinamide: translating nutrition into clinical care. Molecules. 2009, 14: 3446-3485. 10.3390/molecules14093446.PubMedCentralPubMed
75.
go back to reference Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C: Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006, 295: 1681-1687. 10.1001/jama.295.14.1681.PubMed Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C: Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006, 295: 1681-1687. 10.1001/jama.295.14.1681.PubMed
76.
go back to reference Estep PW, Warner JB, Bulyk ML: Short-term calorie restriction in male mice feminizes gene expression and alters key regulators of conserved aging regulatory pathways. PLoS One. 2009, 4: e5242-10.1371/journal.pone.0005242.PubMedCentralPubMed Estep PW, Warner JB, Bulyk ML: Short-term calorie restriction in male mice feminizes gene expression and alters key regulators of conserved aging regulatory pathways. PLoS One. 2009, 4: e5242-10.1371/journal.pone.0005242.PubMedCentralPubMed
77.
go back to reference Chong ZZ, Shang YC, Wang S, Maiese K: SIRT1: New avenues of discovery for disorders of oxidative stress. Expert opinion on therapeutic targets. 2012, 16: 167-178. 10.1517/14728222.2012.648926.PubMedCentralPubMed Chong ZZ, Shang YC, Wang S, Maiese K: SIRT1: New avenues of discovery for disorders of oxidative stress. Expert opinion on therapeutic targets. 2012, 16: 167-178. 10.1517/14728222.2012.648926.PubMedCentralPubMed
78.
79.
go back to reference Kelly GS: A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2. Altern Med Rev. 2010, 15: 313-328.PubMed Kelly GS: A review of the sirtuin system, its clinical implications, and the potential role of dietary activators like resveratrol: part 2. Altern Med Rev. 2010, 15: 313-328.PubMed
80.
go back to reference Maiese K, Chong ZZ, Shang YC, Wang S: Translating cell survival and cell longevity into treatment strategies with SIRT1. Rom J Morphol Embryol. 2011, 52: 1173-1185.PubMedCentralPubMed Maiese K, Chong ZZ, Shang YC, Wang S: Translating cell survival and cell longevity into treatment strategies with SIRT1. Rom J Morphol Embryol. 2011, 52: 1173-1185.PubMedCentralPubMed
81.
go back to reference Orimo M, Minamino T, Miyauchi H, Tateno K, Okada S, Moriya J, Komuro I: Protective role of SIRT1 in diabetic vascular dysfunction. Arterioscler Thromb Vasc Biol. 2009, 29: 889-894. 10.1161/ATVBAHA.109.185694.PubMed Orimo M, Minamino T, Miyauchi H, Tateno K, Okada S, Moriya J, Komuro I: Protective role of SIRT1 in diabetic vascular dysfunction. Arterioscler Thromb Vasc Biol. 2009, 29: 889-894. 10.1161/ATVBAHA.109.185694.PubMed
82.
go back to reference Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, Liu G, Wei YS, Cai H, Liu DP, Liang CC: Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res. 2008, 80: 191-199. 10.1093/cvr/cvn224.PubMedCentralPubMed Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, Liu G, Wei YS, Cai H, Liu DP, Liang CC: Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res. 2008, 80: 191-199. 10.1093/cvr/cvn224.PubMedCentralPubMed
83.
go back to reference Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y: Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem. 2010, 285: 8375-8382. 10.1074/jbc.M109.090266.PubMedCentralPubMed Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K, Horio Y: Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure. J Biol Chem. 2010, 285: 8375-8382. 10.1074/jbc.M109.090266.PubMedCentralPubMed
84.
go back to reference Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isono M, Isshiki K, Uzu T, Kashiwagi A, Koya D: Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med. 2006, 40: 2175-2182. 10.1016/j.freeradbiomed.2006.02.014.PubMed Kume S, Haneda M, Kanasaki K, Sugimoto T, Araki S, Isono M, Isshiki K, Uzu T, Kashiwagi A, Koya D: Silent information regulator 2 (SIRT1) attenuates oxidative stress-induced mesangial cell apoptosis via p53 deacetylation. Free Radic Biol Med. 2006, 40: 2175-2182. 10.1016/j.freeradbiomed.2006.02.014.PubMed
85.
go back to reference Hou J, Wang S, Shang YC, Chong ZZ, Maiese K: Erythropoietin Employs Cell Longevity Pathways of SIRT1 to Foster Endothelial Vascular Integrity During Oxidant Stress. Curr Neurovasc Res. 2011, 8: 220-235. 10.2174/156720211796558069.PubMedCentralPubMed Hou J, Wang S, Shang YC, Chong ZZ, Maiese K: Erythropoietin Employs Cell Longevity Pathways of SIRT1 to Foster Endothelial Vascular Integrity During Oxidant Stress. Curr Neurovasc Res. 2011, 8: 220-235. 10.2174/156720211796558069.PubMedCentralPubMed
86.
go back to reference Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF, Sadoshima J: Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007, 100: 1512-1521. 10.1161/01.RES.0000267723.65696.4a.PubMed Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF, Sadoshima J: Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007, 100: 1512-1521. 10.1161/01.RES.0000267723.65696.4a.PubMed
87.
go back to reference Wang RH, Kim HS, Xiao C, Xu X, Gavrilova O, Deng CX: Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Invest. 2011, 121: 4477-4490. 10.1172/JCI46243.PubMedCentralPubMed Wang RH, Kim HS, Xiao C, Xu X, Gavrilova O, Deng CX: Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J Clin Invest. 2011, 121: 4477-4490. 10.1172/JCI46243.PubMedCentralPubMed
88.
go back to reference Guo W, Qian L, Zhang J, Zhang W, Morrison A, Hayes P, Wilson S, Chen T, Zhao J: Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling. J Neurosci Res. 2011, 89: 1723-1736. 10.1002/jnr.22725.PubMed Guo W, Qian L, Zhang J, Zhang W, Morrison A, Hayes P, Wilson S, Chen T, Zhao J: Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling. J Neurosci Res. 2011, 89: 1723-1736. 10.1002/jnr.22725.PubMed
89.
go back to reference Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009, 460: 392-395.PubMedCentralPubMed Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009, 460: 392-395.PubMedCentralPubMed
90.
go back to reference Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F: Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009, 326: 140-144. 10.1126/science.1177221.PubMed Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F: Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 2009, 326: 140-144. 10.1126/science.1177221.PubMed
91.
go back to reference Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Antoch MP, Blagosklonny MV: Rapamycin extends maximal lifespan in cancer-prone mice. Am J Pathol. 2010, 176: 2092-2097. 10.2353/ajpath.2010.091050.PubMedCentralPubMed Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Antoch MP, Blagosklonny MV: Rapamycin extends maximal lifespan in cancer-prone mice. Am J Pathol. 2010, 176: 2092-2097. 10.2353/ajpath.2010.091050.PubMedCentralPubMed
92.
go back to reference Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand-Brustel Y, Klumperman J, Thorens B, Thomas G: Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature. 2000, 408: 994-997. 10.1038/35050135.PubMed Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand-Brustel Y, Klumperman J, Thorens B, Thomas G: Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature. 2000, 408: 994-997. 10.1038/35050135.PubMed
93.
go back to reference Hamada S, Hara K, Hamada T, Yasuda H, Moriyama H, Nakayama R, Nagata M, Yokono K: Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia. Diabetes. 2009, 58: 1321-1332. 10.2337/db08-0519.PubMedCentralPubMed Hamada S, Hara K, Hamada T, Yasuda H, Moriyama H, Nakayama R, Nagata M, Yokono K: Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia. Diabetes. 2009, 58: 1321-1332. 10.2337/db08-0519.PubMedCentralPubMed
94.
go back to reference Fraenkel M, Ketzinel-Gilad M, Ariav Y, Pappo O, Karaca M, Castel J, Berthault MF, Magnan C, Cerasi E, Kaiser N, Leibowitz G: mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes. 2008, 57: 945-957. 10.2337/db07-0922.PubMed Fraenkel M, Ketzinel-Gilad M, Ariav Y, Pappo O, Karaca M, Castel J, Berthault MF, Magnan C, Cerasi E, Kaiser N, Leibowitz G: mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes. 2008, 57: 945-957. 10.2337/db07-0922.PubMed
95.
go back to reference Deblon N, Bourgoin L, Veyrat-Durebex C, Peyrou M, Vinciguerra M, Caillon A, Maeder C, Fournier M, Montet X, Rohner-Jeanrenaud F, Foti M: Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br J Pharmacol. 2011, 165: 2325-2340. Deblon N, Bourgoin L, Veyrat-Durebex C, Peyrou M, Vinciguerra M, Caillon A, Maeder C, Fournier M, Montet X, Rohner-Jeanrenaud F, Foti M: Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br J Pharmacol. 2011, 165: 2325-2340.
96.
go back to reference Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, Barnett J, Leslie NR, Cheng S, Shepherd PR: The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004, 166: 213-223. 10.1083/jcb.200403069.PubMedCentralPubMed Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, Barnett J, Leslie NR, Cheng S, Shepherd PR: The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004, 166: 213-223. 10.1083/jcb.200403069.PubMedCentralPubMed
97.
go back to reference 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. 2005, 146: 1473-1481.PubMed 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. 2005, 146: 1473-1481.PubMed
98.
go back to reference Kim JA, Jang HJ, Martinez-Lemus LA, Sowers JR: Activation of mTOR/p70S6 Kinase by ANG II Inhibits Insulin Stimulated Endothelial Nitric Oxide Synthase and Vasodilation. Am J Physiol Endocrinol Metab. 2011, 302: E201-208.PubMedCentralPubMed Kim JA, Jang HJ, Martinez-Lemus LA, Sowers JR: Activation of mTOR/p70S6 Kinase by ANG II Inhibits Insulin Stimulated Endothelial Nitric Oxide Synthase and Vasodilation. Am J Physiol Endocrinol Metab. 2011, 302: E201-208.PubMedCentralPubMed
99.
go back to reference Inoki K, Zhu T, Guan KL: TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003, 115: 577-590. 10.1016/S0092-8674(03)00929-2.PubMed Inoki K, Zhu T, Guan KL: TSC2 mediates cellular energy response to control cell growth and survival. Cell. 2003, 115: 577-590. 10.1016/S0092-8674(03)00929-2.PubMed
100.
go back to reference Paiva MA, Rutter-Locher Z, Goncalves LM, Providencia LA, Davidson SM, Yellon DM, Mocanu MM: Enhancing AMPK activation during ischemia protects the diabetic heart against reperfusion injury. Am J Physiol Heart Circ Physiol. 2011, 300: H2123-2134. 10.1152/ajpheart.00707.2010.PubMedCentralPubMed Paiva MA, Rutter-Locher Z, Goncalves LM, Providencia LA, Davidson SM, Yellon DM, Mocanu MM: Enhancing AMPK activation during ischemia protects the diabetic heart against reperfusion injury. Am J Physiol Heart Circ Physiol. 2011, 300: H2123-2134. 10.1152/ajpheart.00707.2010.PubMedCentralPubMed
101.
go back to reference Saha AK, Xu XJ, Lawson E, Deoliveira R, Brandon AE, Kraegen EW, Ruderman NB: Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes. 2010, 59: 2426-2434. 10.2337/db09-1870.PubMedCentralPubMed Saha AK, Xu XJ, Lawson E, Deoliveira R, Brandon AE, Kraegen EW, Ruderman NB: Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes. 2010, 59: 2426-2434. 10.2337/db09-1870.PubMedCentralPubMed
102.
go back to reference Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004, 101: 3329-3335. 10.1073/pnas.0308061100.PubMedCentralPubMed Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA, Cantley LC: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci U S A. 2004, 101: 3329-3335. 10.1073/pnas.0308061100.PubMedCentralPubMed
103.
go back to reference Jessen N, Koh HJ, Folmes CD, Wagg C, Fujii N, Lofgren B, Wolf CM, Berul CI, Hirshman MF, Lopaschuk GD, Goodyear LJ: Ablation of LKB1 in the heart leads to energy deprivation and impaired cardiac function. Biochim Biophys Acta. 2010, 1802: 593-600. 10.1016/j.bbadis.2010.04.008.PubMedCentralPubMed Jessen N, Koh HJ, Folmes CD, Wagg C, Fujii N, Lofgren B, Wolf CM, Berul CI, Hirshman MF, Lopaschuk GD, Goodyear LJ: Ablation of LKB1 in the heart leads to energy deprivation and impaired cardiac function. Biochim Biophys Acta. 2010, 1802: 593-600. 10.1016/j.bbadis.2010.04.008.PubMedCentralPubMed
104.
go back to reference Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature. 2001, 409: 307-312. 10.1038/35053000.PubMed Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA: The hormone resistin links obesity to diabetes. Nature. 2001, 409: 307-312. 10.1038/35053000.PubMed
105.
go back to reference Kang S, Chemaly ER, Hajjar RJ, Lebeche D: Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways. J Biol Chem. 2011, 286: 18465-18473. 10.1074/jbc.M110.200022.PubMedCentralPubMed Kang S, Chemaly ER, Hajjar RJ, Lebeche D: Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways. J Biol Chem. 2011, 286: 18465-18473. 10.1074/jbc.M110.200022.PubMedCentralPubMed
106.
go back to reference Shan J, Nguyen TB, Totary-Jain H, Dansky H, Marx SO, Marks AR: Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. Proc Natl Acad Sci U S A. 2008, 105: 19006-19011. 10.1073/pnas.0809743105.PubMedCentralPubMed Shan J, Nguyen TB, Totary-Jain H, Dansky H, Marx SO, Marks AR: Leptin-enhanced neointimal hyperplasia is reduced by mTOR and PI3K inhibitors. Proc Natl Acad Sci U S A. 2008, 105: 19006-19011. 10.1073/pnas.0809743105.PubMedCentralPubMed
107.
go back to reference Pasini E, Flati V, Paiardi S, Rizzoni D, Porteri E, Aquilani R, Assanelli D, Corsetti G, Speca S, Rezzani R: Intracellular molecular effects of insulin resistance in patients with metabolic syndrome. Cardiovasc Diabetol. 2010, 9: 46-10.1186/1475-2840-9-46.PubMedCentralPubMed Pasini E, Flati V, Paiardi S, Rizzoni D, Porteri E, Aquilani R, Assanelli D, Corsetti G, Speca S, Rezzani R: Intracellular molecular effects of insulin resistance in patients with metabolic syndrome. Cardiovasc Diabetol. 2010, 9: 46-10.1186/1475-2840-9-46.PubMedCentralPubMed
108.
go back to reference Medeiros C, Frederico MJ, da Luz G, Pauli JR, Silva AS, Pinho RA, Velloso LA, Ropelle ER, De Souza CT: Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet-induced obesity rats. J Cell Physiol. 2011, 226: 666-674. 10.1002/jcp.22387.PubMed Medeiros C, Frederico MJ, da Luz G, Pauli JR, Silva AS, Pinho RA, Velloso LA, Ropelle ER, De Souza CT: Exercise training reduces insulin resistance and upregulates the mTOR/p70S6k pathway in cardiac muscle of diet-induced obesity rats. J Cell Physiol. 2011, 226: 666-674. 10.1002/jcp.22387.PubMed
109.
go back to reference Wang B, Atherton P, Patel R, Manning G, Donnelly R: Antiangiogenic effects and transcriptional regulation of pigment epithelium-derived factor in diabetic retinopathy. Microvasc Res. 2010, 80: 31-36. 10.1016/j.mvr.2010.02.012.PubMed Wang B, Atherton P, Patel R, Manning G, Donnelly R: Antiangiogenic effects and transcriptional regulation of pigment epithelium-derived factor in diabetic retinopathy. Microvasc Res. 2010, 80: 31-36. 10.1016/j.mvr.2010.02.012.PubMed
110.
go back to reference Xue Q, Nagy JA, Manseau EJ, Phung TL, Dvorak HF, Benjamin LE: Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking S6Kinase. Arterioscler Thromb Vasc Biol. 2009, 29: 1172-1178. 10.1161/ATVBAHA.109.185918.PubMedCentralPubMed Xue Q, Nagy JA, Manseau EJ, Phung TL, Dvorak HF, Benjamin LE: Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking S6Kinase. Arterioscler Thromb Vasc Biol. 2009, 29: 1172-1178. 10.1161/ATVBAHA.109.185918.PubMedCentralPubMed
111.
go back to reference Roulin D, Cerantola Y, Dormond-Meuwly A, Demartines N, Dormond O: Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo. Mol Cancer. 2010, 9: 57.PubMedCentralPubMed Roulin D, Cerantola Y, Dormond-Meuwly A, Demartines N, Dormond O: Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo. Mol Cancer. 2010, 9: 57.PubMedCentralPubMed
112.
go back to reference Chong ZZ, Li F, Maiese K: The pro-survival pathways of mTOR and protein kinase B target glycogen synthase kinase-3beta and nuclear factor-kappaB to foster endogenous microglial cell protection. Int J Mol Med. 2007, 19: 263-272.PubMedCentralPubMed Chong ZZ, Li F, Maiese K: The pro-survival pathways of mTOR and protein kinase B target glycogen synthase kinase-3beta and nuclear factor-kappaB to foster endogenous microglial cell protection. Int J Mol Med. 2007, 19: 263-272.PubMedCentralPubMed
113.
go back to reference Dello Russo C, Lisi L, Tringali G, Navarra P: Involvement of mTOR kinase in cytokine-dependent microglial activation and cell proliferation. Biochem Pharmacol. 2009, 78: 1242-1251. 10.1016/j.bcp.2009.06.097.PubMed Dello Russo C, Lisi L, Tringali G, Navarra P: Involvement of mTOR kinase in cytokine-dependent microglial activation and cell proliferation. Biochem Pharmacol. 2009, 78: 1242-1251. 10.1016/j.bcp.2009.06.097.PubMed
114.
go back to reference Poulose SM, Bielinski DF, Carrihill-Knoll K, Rabin BM, Shukitt-Hale B: Exposure to (16)O-Particle Radiation Causes Aging-Like Decrements in Rats through Increased Oxidative Stress, Inflammation and Loss of Autophagy. Radiat Res. 2011, 176: 761-769. 10.1667/RR2605.1.PubMed Poulose SM, Bielinski DF, Carrihill-Knoll K, Rabin BM, Shukitt-Hale B: Exposure to (16)O-Particle Radiation Causes Aging-Like Decrements in Rats through Increased Oxidative Stress, Inflammation and Loss of Autophagy. Radiat Res. 2011, 176: 761-769. 10.1667/RR2605.1.PubMed
115.
go back to reference Shang YC, Chong ZZ, Wang S, Maiese K: Erythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia. Curr Neurovasc Res. 2011, 8: 270-285. 10.2174/156720211798120990.PubMedCentralPubMed Shang YC, Chong ZZ, Wang S, Maiese K: Erythropoietin and Wnt1 Govern Pathways of mTOR, Apaf-1, and XIAP in Inflammatory Microglia. Curr Neurovasc Res. 2011, 8: 270-285. 10.2174/156720211798120990.PubMedCentralPubMed
116.
go back to reference Shang YC, Chong ZZ, Wang S, Maiese K: Prevention of beta-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL. Aging (Albany NY). 2012, 4: 187-201. Shang YC, Chong ZZ, Wang S, Maiese K: Prevention of beta-amyloid degeneration of microglia by erythropoietin depends on Wnt1, the PI 3-K/mTOR pathway, Bad, and Bcl-xL. Aging (Albany NY). 2012, 4: 187-201.
Metadata
Title
Mammalian target of rapamycin signaling in diabetic cardiovascular disease
Authors
Zhao Zhong Chong
Kenneth Maiese
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2012
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-11-45

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