Journal of Molecular and Cellular Cardiology
Volume 49, Issue 6 , Pages 931-940 , December 2010

Akt2 deficiency promotes cardiac induction of Rab4a and myocardial β-adrenergic hypersensitivity

  • Sharon Etzion

      Affiliations

    • Center for Cardiovascular Research, John Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
    • ,
  • Yoram Etzion

      Affiliations

    • Center for Cardiovascular Research, John Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
    • ,
  • Brian DeBosch

      Affiliations

    • Center for Cardiovascular Research, John Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
    • ,
  • Peter A. Crawford

      Affiliations

    • Center for Cardiovascular Research, John Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
    • ,
  • Anthony J. Muslin

      Affiliations

    • Center for Cardiovascular Research, John Milliken Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
    • Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA
    • Corresponding Author InformationCorresponding author. Center for Cardiovascular Research, Washington University School of Medicine, Box 8086, 660 South Euclid Avenue, St. Louis, MO 63110, USA. Fax: +1 314 747 3545.

Received 16 July 2010 ,Revised 12 August 2010 ,Accepted 12 August 2010.

References 

  1. Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet. May 24 2008;371(9626):1800–1809
  2. Cohen-Solal A, Beauvais F, Logeart D. Heart failure and diabetes mellitus: epidemiology and management of an alarming association. J Card Fail. Sep 2008;14(7):615–625
  3. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation. Jun 26 2007;115(25):3213–3223
  4. Zaid H, Antonescu CN, Randhawa VK, Klip A. Insulin action on glucose transporters through molecular switches, tracks and tethers. Biochem J. Jul 15 2008;413(2):201–215
  5. Cantley LC. The phosphoinositide 3-kinase pathway. Science. May 31 2002;296(5573):1655–1657
  6. Farese RV, Sajan MP, Standaert ML. Insulin-sensitive protein kinases (atypical protein kinase C and protein kinase B/Akt): actions and defects in obesity and type II diabetes. Exp Biol Med (Maywood). Oct 2005;230(9):593–605
  7. Lehman JJ, Kelly DP. Gene regulatory mechanisms governing energy metabolism during cardiac hypertrophic growth. Heart Fail Rev. Apr 2002;7(2):175–185
  8. Yamada E, Okada S, Saito T, Ohshima K, Sato M, Tsuchiya T, et al. Akt2 phosphorylates Synip to regulate docking and fusion of GLUT4-containing vesicles. J Cell Biol. Mar 14 2005;168(6):921–928
  9. Sano H, Kane S, Sano E, Miinea CP, Asara JM, Lane WS, et al. Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation. J Biol Chem. Apr 25 2003;278(17):14599–14602
  10. Aledo JC, Darakhshan F, Hundal HS. Rab4, but not the transferrin receptor, is colocalized with GLUT4 in an insulin-sensitive intracellular compartment in rat skeletal muscle. Biochem Biophys Res Commun. Oct 4 1995;215(1):321–328
  11. Dransfeld O, Uphues I, Sasson S, Schurmann A, Joost HG, Eckel J. Regulation of subcellular distribution of GLUT4 in cardiomyocytes: Rab4A reduces basal glucose transport and augments insulin responsiveness. Exp Clin Endocrinol Diabetes. 2000;108(1):26–36
  12. Burgering BM. A brief introduction to FOXOlogy. Oncogene. Apr 7 2008;27(16):2258–2262
  13. Cho H, Thorvaldsen JL, Chu Q, Feng F, Birnbaum MJ. Akt1/PKBalpha is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J Biol Chem. Oct 19 2001;276(42):38349–38352
  14. Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Crenshaw EB, et al. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science. Jun 1 2001;292(5522):1728–1731
  15. George S, Rochford JJ, Wolfrum C, Gray SL, Schinner S, Wilson JC, et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2. Science. May 28 2004;304(5675):1325–1328
  16. Sasso FC, Torella D, Carbonara O, Ellison GM, Torella M, Scardone M, et al. Increased vascular endothelial growth factor expression but impaired vascular endothelial growth factor receptor signaling in the myocardium of type 2 diabetic patients with chronic coronary heart disease. J Am Coll Cardiol. Sep 6 2005;46(5):827–834
  17. DeBosch B, Sambandam N, Weinheimer C, Courtois M, Muslin AJ. Akt2 regulates cardiac metabolism and cardiomyocyte survival. J Biol Chem. Oct 27 2006;281(43):32841–32851
  18. Filipeanu CM, Zhou F, Lam ML, Kerut KE, Claycomb WC, Wu G. Enhancement of the recycling and activation of beta-adrenergic receptor by Rab4 GTPase in cardiac myocytes. J Biol Chem. Apr 21 2006;281(16):11097–11103
  19. Odley A, Hahn HS, Lynch RA, Marreez Y, Osinska H, Robbins J, et al. Regulation of cardiac contractility by Rab4-modulated beta2-adrenergic receptor recycling. Proc Natl Acad Sci U S A. May 4 2004;101(18):7082–7087
  20. Finck BN, Lehman JJ, Leone TC, Welch MJ, Bennett MJ, Kovacs A, et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. Jan 2002;109(1):121–130
  21. Asai K, Yang GP, Geng YJ, Takagi G, Bishop S, Ishikawa Y, et al. Beta-adrenergic receptor blockade arrests myocyte damage and preserves cardiac function in the transgenic G(salpha) mouse. J Clin Invest. Sep 1999;104(5):551–558
  22. Seachrist JL, Anborgh PH, Ferguson SS. beta 2-adrenergic receptor internalization, endosomal sorting, and plasma membrane recycling are regulated by rab GTPases. J Biol Chem. Sep 1 2000;275(35):27221–27228
  23. Ni YG, Wang N, Cao DJ, Sachan N, Morris DJ, Gerard RD, et al. FoxO transcription factors activate Akt and attenuate insulin signaling in heart by inhibiting protein phosphatases. Proc Natl Acad Sci U S A. Dec 18 2007;104(51):20517–20522
  24. Metrich M, Lucas A, Gastineau M, Samuel JL, Heymes C, Morel E, et al. Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy. Circ Res. Apr 25 2008;102(8):959–965
  25. Ulucan C, Wang X, Baljinnyam E, Bai Y, Okumura S, Sato M, et al. Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy. Am J Physiol Heart Circ Physiol. Sep 2007;293(3):H1662–H1672
  26. Park SY, Cho YR, Finck BN, Kim HJ, Higashimori T, Hong EG, et al. Cardiac-specific overexpression of peroxisome proliferator-activated receptor-alpha causes insulin resistance in heart and liver. Diabetes. Sep 2005;54(9):2514–2524
  27. Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmembrane-spanning receptors and heart function. Nature. Jan 10 2002;415(6868):206–212
  28. Choi DJ, Koch WJ, Hunter JJ, Rockman HA. Mechanism of beta-adrenergic receptor desensitization in cardiac hypertrophy is increased beta-adrenergic receptor kinase. J Biol Chem. Jul 4 1997;272(27):17223–17229
  29. Lohse MJ. Molecular mechanisms of membrane receptor desensitization. Biochim Biophys Acta. Nov 7 1993;1179(2):171–188
  30. Saadane N, Alpert L, Chalifour LE. Expression of immediate early genes, GATA-4, and Nkx-2.5 in adrenergic-induced cardiac hypertrophy and during regression in adult mice. Br J Pharmacol. Jul 1999;127(5):1165–1176
  31. Hohimer AR, Davis LE, Hatton DC. Repeated daily injections and osmotic pump infusion of isoproterenol cause similar increases in cardiac mass but have different effects on blood pressure. Can J Physiol Pharmacol. Feb 2005;83(2):191–197
  32. Kudej RK, Iwase M, Uechi M, Vatner DE, Oka N, Ishikawa Y, et al. Effects of chronic beta-adrenergic receptor stimulation in mice. J Mol Cell Cardiol. Oct 1997;29(10):2735–2746
  33. Faulx MD, Ernsberger P, Vatner D, Hoffman RD, Lewis W, Strachan R, et al. Strain-dependent beta-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice. Am J Physiol Heart Circ Physiol. Jul 2005;289(1):H30–H36
  34. Cormont M, Gautier N, Ilc K, le Marchand-Brustel Y. Expression of a prenylation-deficient Rab4 inhibits the GLUT4 translocation induced by active phosphatidylinositol 3-kinase and protein kinase B. Biochem J. May 15 2001;356(Pt 1):143–149
  35. Vollenweider P, Martin SS, Haruta T, Morris AJ, Nelson JG, Cormont M, et al. The small guanosine triphosphate-binding protein Rab4 is involved in insulin-induced GLUT4 translocation and actin filament rearrangement in 3T3-L1 cells. Endocrinology. Nov 1997;138(11):4941–4949
  36. Li X, Monks B, Ge Q, Birnbaum MJ. Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator. Nature. Jun 21 2007;447(7147):1012–1016
  37. Harris IS, Treskov I, Rowley MW, Heximer S, Kaltenbronn K, Finck BN, et al. G-protein signaling participates in the development of diabetic cardiomyopathy. Diabetes. Dec 2004;53(12):3082–3090
  38. Loichot C, Jesel L, Tesse A, Tabernero A, Schoonjans K, Roul G, et al. Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions. Am J Physiol Heart Circ Physiol. Jul 2006;291(1):H161–H166
  39. Dorn GW, Liggett SB. Mechanisms of pharmacogenomic effects of genetic variation within the cardiac adrenergic network in heart failure. Mol Pharmacol. Sep 2009;76(3):466–480
  40. Liggett SB, Cresci S, Kelly RJ, Syed FM, Matkovich SJ, Hahn HS, et al. A GRK5 polymorphism that inhibits beta-adrenergic receptor signaling is protective in heart failure. Nat Med. May 2008;14(5):510–517
  41. Landray MJ, Toescu V, Kendall MJ. The cardioprotective role of beta-blockers in patients with diabetes mellitus. J Clin Pharm Ther. Aug 2002;27(4):233–242
  42. Di Bari M, Marchionni N, Pahor M. Beta-blockers after acute myocardial infarction in elderly patients with diabetes mellitus: time to reassess. Drugs Aging. 2003;20(1):13–22
  43. Haas SJ, Vos T, Gilbert RE, Krum H. Are beta-blockers as efficacious in patients with diabetes mellitus as in patients without diabetes mellitus who have chronic heart failure? A meta-analysis of large-scale clinical trials. Am Heart J. Nov 2003;146(5):848–853
  44. Hata JA, Williams ML, Schroder JN, Lima B, Keys JR, Blaxall BC, et al. Lymphocyte levels of GRK2 (betaARK1) mirror changes in the LVAD-supported failing human heart: lower GRK2 associated with improved beta-adrenergic signaling after mechanical unloading. J Card Fail. Jun 2006;12(5):360–368
  45. Iaccarino G, Barbato E, Cipolletta E, De Amicis V, Margulies KB, Leosco D, et al. Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure. Eur Heart J. Sep 2005;26(17):1752–1758

PII: S0022-2828(10)00298-1

doi: 10.1016/j.yjmcc.2010.08.011

Journal of Molecular and Cellular Cardiology
Volume 49, Issue 6 , Pages 931-940 , December 2010

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