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. 1996 May 1;315(Pt 3):875–882. doi: 10.1042/bj3150875

Roles of insulin, guanosine 5'-[gamma-thio]triphosphate and phorbol 12-myristate 13-acetate in signalling pathways of GLUT4 translocation.

M Todaka 1, H Hayashi 1, T Imanaka 1, Y Mitani 1, S Kamohara 1, K Kishi 1, K Tamaoka 1, F Kanai 1, M Shichiri 1, N Morii 1, S Narumiya 1, Y Ebina 1
PMCID: PMC1217288  PMID: 8645171

Abstract

Insulin, guanosine 5'-[gamma-thio]triphosphate (GTP[S] and phorbol 12-myristate 13-acetate (PMA) trigger the translocation of Gl UT4 (type 4 glucose transporter; insulin-sensitive glucose transporter) from an intracellular pool to the cell surface. We have developed a highly sensitive and quantitative method to detect GLUT4 immunologically on the surface of intact 3T3-L1 adipocytes and Chinese hamster ovary (CHO) cells, using c-myc epitope-tagged GLUT4 (GLUT4myc). We examined the roles of insulin, GTP[S] and PMA in the signalling pathways of GLUT4 translocation in the CHO cell system. Among small molecular GTP-binding proteins, ras, rab3D, rad and rho seem to be candidates as signal transmitters of insulin-stimulated GLUT4 translocation. Overexpression of wild-type H-ras and the dominant negative mutant H-rass17N in our cell system respectively enhanced and blocked insulin-stimulated activation of mitogen-activated protein kinase, but did not affect insulin-stimulated GLUT4 translocation. Overexpression of rab3D or rad in the cells did not affect GLUT4 translocation triggered by insulin, GTP[S] or PMA. Treatment with Botulinum C3 exoenzyme, a specific inhibitor of rho, had no effect on GLUT4 translocation induced by insulin, GTP[S] or PMA. Therefore these small molecular GTP-binding proteins are not likely to be involved in GLUT4 translocation. In addition, insulin, GTP[S] and PMA apparently stimulate GLUT4 translocation through independent pathways.

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Selected References

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  1. Ando A., Yonezawa K., Gout I., Nakata T., Ueda H., Hara K., Kitamura Y., Noda Y., Takenawa T., Hirokawa N. A complex of GRB2-dynamin binds to tyrosine-phosphorylated insulin receptor substrate-1 after insulin treatment. EMBO J. 1994 Jul 1;13(13):3033–3038. doi: 10.1002/j.1460-2075.1994.tb06602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baldini G., Hohl T., Lin H. Y., Lodish H. F. Cloning of a Rab3 isotype predominantly expressed in adipocytes. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5049–5052. doi: 10.1073/pnas.89.11.5049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baldini G., Hohman R., Charron M. J., Lodish H. F. Insulin and nonhydrolyzable GTP analogs induce translocation of GLUT 4 to the plasma membrane in alpha-toxin-permeabilized rat adipose cells. J Biol Chem. 1991 Mar 5;266(7):4037–4040. [PubMed] [Google Scholar]
  4. Blackmore P. F., Bocckino S. B., Waynick L. E., Exton J. H. Role of a guanine nucleotide-binding regulatory protein in the hydrolysis of hepatocyte phosphatidylinositol 4,5-bisphosphate by calcium-mobilizing hormones and the control of cell calcium. Studies utilizing aluminum fluoride. J Biol Chem. 1985 Nov 25;260(27):14477–14483. [PubMed] [Google Scholar]
  5. Burgering B. M., Pronk G. J., van Weeren P. C., Chardin P., Bos J. L. cAMP antagonizes p21ras-directed activation of extracellular signal-regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor. EMBO J. 1993 Nov;12(11):4211–4220. doi: 10.1002/j.1460-2075.1993.tb06105.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Calderhead D. M., Kitagawa K., Tanner L. I., Holman G. D., Lienhard G. E. Insulin regulation of the two glucose transporters in 3T3-L1 adipocytes. J Biol Chem. 1990 Aug 15;265(23):13801–13808. [PubMed] [Google Scholar]
  7. Cheatham B., Vlahos C. J., Cheatham L., Wang L., Blenis J., Kahn C. R. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation. Mol Cell Biol. 1994 Jul;14(7):4902–4911. doi: 10.1128/mcb.14.7.4902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clark A. E., Holman G. D. Exofacial photolabelling of the human erythrocyte glucose transporter with an azitrifluoroethylbenzoyl-substituted bismannose. Biochem J. 1990 Aug 1;269(3):615–622. doi: 10.1042/bj2690615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clarke J. F., Young P. W., Yonezawa K., Kasuga M., Holman G. D. Inhibition of the translocation of GLUT1 and GLUT4 in 3T3-L1 cells by the phosphatidylinositol 3-kinase inhibitor, wortmannin. Biochem J. 1994 Jun 15;300(Pt 3):631–635. doi: 10.1042/bj3000631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cushman S. W., Wardzala L. J. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane. J Biol Chem. 1980 May 25;255(10):4758–4762. [PubMed] [Google Scholar]
  11. Fischer von Mollard G., Stahl B., Li C., Südhof T. C., Jahn R. Rab proteins in regulated exocytosis. Trends Biochem Sci. 1994 Apr;19(4):164–168. doi: 10.1016/0968-0004(94)90278-x. [DOI] [PubMed] [Google Scholar]
  12. Gould G. W., Jess T. J., Andrews G. C., Herbst J. J., Plevin R. J., Gibbs E. M. Evidence for a role of phosphatidylinositol 3-kinase in the regulation of glucose transport in Xenopus oocytes. J Biol Chem. 1994 Oct 28;269(43):26622–26625. [PubMed] [Google Scholar]
  13. Gould G. W., Merrall N. W., Martin S., Jess T. J., Campbell I. W., Calderhead D. M., Gibbs E. M., Holman G. D., Plevin R. J. Growth factor-induced stimulation of hexose transport in 3T3-L1 adipocytes: evidence that insulin-induced translocation of GLUT4 is independent of activation of MAP kinase. Cell Signal. 1994 Mar;6(3):313–320. doi: 10.1016/0898-6568(94)90036-1. [DOI] [PubMed] [Google Scholar]
  14. Hara K., Yonezawa K., Sakaue H., Ando A., Kotani K., Kitamura T., Kitamura Y., Ueda H., Stephens L., Jackson T. R. 1-Phosphatidylinositol 3-kinase activity is required for insulin-stimulated glucose transport but not for RAS activation in CHO cells. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7415–7419. doi: 10.1073/pnas.91.16.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hausdorff S. F., Frangioni J. V., Birnbaum M. J. Role of p21ras in insulin-stimulated glucose transport in 3T3-L1 adipocytes. J Biol Chem. 1994 Aug 26;269(34):21391–21394. [PubMed] [Google Scholar]
  16. Hayashi H., Kamohara S., Nishioka Y., Kanai F., Miyake N., Fukui Y., Shibasaki F., Takenawa T., Ebina Y. Insulin treatment stimulates the tyrosine phosphorylation of the alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase in vivo. J Biol Chem. 1992 Nov 5;267(31):22575–22580. [PubMed] [Google Scholar]
  17. Hayashi H., Nishioka Y., Kamohara S., Kanai F., Ishii K., Fukui Y., Shibasaki F., Takenawa T., Kido H., Katsunuma N. The alpha-type 85-kDa subunit of phosphatidylinositol 3-kinase is phosphorylated at tyrosines 368, 580, and 607 by the insulin receptor. J Biol Chem. 1993 Apr 5;268(10):7107–7117. [PubMed] [Google Scholar]
  18. Hayashi H., Owada M. K., Sonobe S., Kakunaga T. Characterizations of two distinct Ca2+-dependent phospholipid-binding proteins of 68-kDa isolated from human placenta. J Biol Chem. 1989 Oct 15;264(29):17222–17230. [PubMed] [Google Scholar]
  19. Ishii K., Hayashi H., Todaka M., Kamohara S., Kanai F., Jinnouchi H., Wang L., Ebina Y. Possible domains responsible for intracellular targeting and insulin-dependent translocation of glucose transporter type 4. Biochem J. 1995 Aug 1;309(Pt 3):813–823. doi: 10.1042/bj3090813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ishii K., Kamohara S., Hayashi H., Todaka M., Kanai F., Imanaka T., Ebina Y. Epidermal growth factor triggers the translocation of insulin-responsive glucose transporter (GLUT4). Biochem Biophys Res Commun. 1994 Nov 30;205(1):857–863. doi: 10.1006/bbrc.1994.2743. [DOI] [PubMed] [Google Scholar]
  21. Kahn C. R. Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes. Diabetes. 1994 Aug;43(8):1066–1084. doi: 10.2337/diab.43.8.1066. [DOI] [PubMed] [Google Scholar]
  22. Kamohara S., Hayashi H., Todaka M., Kanai F., Ishii K., Imanaka T., Escobedo J. A., Williams L. T., Ebina Y. Platelet-derived growth factor triggers translocation of the insulin-regulatable glucose transporter (type 4) predominantly through phosphatidylinositol 3-kinase binding sites on the receptor. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1077–1081. doi: 10.1073/pnas.92.4.1077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kanai F., Ito K., Todaka M., Hayashi H., Kamohara S., Ishii K., Okada T., Hazeki O., Ui M., Ebina Y. Insulin-stimulated GLUT4 translocation is relevant to the phosphorylation of IRS-1 and the activity of PI3-kinase. Biochem Biophys Res Commun. 1993 Sep 15;195(2):762–768. doi: 10.1006/bbrc.1993.2111. [DOI] [PubMed] [Google Scholar]
  24. Kanai F., Nishioka Y., Hayashi H., Kamohara S., Todaka M., Ebina Y. Direct demonstration of insulin-induced GLUT4 translocation to the surface of intact cells by insertion of a c-myc epitope into an exofacial GLUT4 domain. J Biol Chem. 1993 Jul 5;268(19):14523–14526. [PubMed] [Google Scholar]
  25. Kozma L., Baltensperger K., Klarlund J., Porras A., Santos E., Czech M. P. The ras signaling pathway mimics insulin action on glucose transporter translocation. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4460–4464. doi: 10.1073/pnas.90.10.4460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kuhné M. R., Pawson T., Lienhard G. E., Feng G. S. The insulin receptor substrate 1 associates with the SH2-containing phosphotyrosine phosphatase Syp. J Biol Chem. 1993 Jun 5;268(16):11479–11481. [PubMed] [Google Scholar]
  27. Lee C. H., Li W., Nishimura R., Zhou M., Batzer A. G., Myers M. G., Jr, White M. F., Schlessinger J., Skolnik E. Y. Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11713–11717. doi: 10.1073/pnas.90.24.11713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Manchester J., Kong X., Lowry O. H., Lawrence J. C., Jr Ras signaling in the activation of glucose transport by insulin. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4644–4648. doi: 10.1073/pnas.91.11.4644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Matsui Y., Kikuchi A., Araki S., Hata Y., Kondo J., Teranishi Y., Takai Y. Molecular cloning and characterization of a novel type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding protein. Mol Cell Biol. 1990 Aug;10(8):4116–4122. doi: 10.1128/mcb.10.8.4116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Merrall N. W., Plevin R. J., Stokoe D., Cohen P., Nebreda A. R., Gould G. W. Mitogen-activated protein kinase (MAP kinase), MAP kinase kinase and c-Mos stimulate glucose transport in Xenopus oocytes. Biochem J. 1993 Oct 15;295(Pt 2):351–355. doi: 10.1042/bj2950351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Myers M. G., Jr, Backer J. M., Sun X. J., Shoelson S., Hu P., Schlessinger J., Yoakim M., Schaffhausen B., White M. F. IRS-1 activates phosphatidylinositol 3'-kinase by associating with src homology 2 domains of p85. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10350–10354. doi: 10.1073/pnas.89.21.10350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Myers M. G., Jr, Sun X. J., White M. F. The IRS-1 signaling system. Trends Biochem Sci. 1994 Jul;19(7):289–293. doi: 10.1016/0968-0004(94)90007-8. [DOI] [PubMed] [Google Scholar]
  33. Mühlbacher C., Karnieli E., Schaff P., Obermaier B., Mushack J., Rattenhuber E., Häring H. U. Phorbol esters imitate in rat fat-cells the full effect of insulin on glucose-carrier translocation, but not on 3-O-methylglucose-transport activity. Biochem J. 1988 Feb 1;249(3):865–870. doi: 10.1042/bj2490865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nakanishi H., Brewer K. A., Exton J. H. Activation of the zeta isozyme of protein kinase C by phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem. 1993 Jan 5;268(1):13–16. [PubMed] [Google Scholar]
  35. Nemoto Y., Namba T., Kozaki S., Narumiya S. Clostridium botulinum C3 ADP-ribosyltransferase gene. Cloning, sequencing, and expression of a functional protein in Escherichia coli. J Biol Chem. 1991 Oct 15;266(29):19312–19319. [PubMed] [Google Scholar]
  36. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
  37. Obermaier-Kusser B., Mühlbacher C., Mushack J., Rattenhuber E., Fehlmann M., Haring H. U. Regulation of glucose carrier activity by AlCl3 and phospholipase C in fat-cells. Biochem J. 1988 Dec 1;256(2):515–520. doi: 10.1042/bj2560515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Okada T., Kawano Y., Sakakibara T., Hazeki O., Ui M. Essential role of phosphatidylinositol 3-kinase in insulin-induced glucose transport and antilipolysis in rat adipocytes. Studies with a selective inhibitor wortmannin. J Biol Chem. 1994 Feb 4;269(5):3568–3573. [PubMed] [Google Scholar]
  39. Paterson H. F., Self A. J., Garrett M. D., Just I., Aktories K., Hall A. Microinjection of recombinant p21rho induces rapid changes in cell morphology. J Cell Biol. 1990 Sep;111(3):1001–1007. doi: 10.1083/jcb.111.3.1001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Piper R. C., Hess L. J., James D. E. Differential sorting of two glucose transporters expressed in insulin-sensitive cells. Am J Physiol. 1991 Mar;260(3 Pt 1):C570–C580. doi: 10.1152/ajpcell.1991.260.3.C570. [DOI] [PubMed] [Google Scholar]
  41. Quon M. J., Chen H., Ing B. L., Liu M. L., Zarnowski M. J., Yonezawa K., Kasuga M., Cushman S. W., Taylor S. I. Roles of 1-phosphatidylinositol 3-kinase and ras in regulating translocation of GLUT4 in transfected rat adipose cells. Mol Cell Biol. 1995 Oct;15(10):5403–5411. doi: 10.1128/mcb.15.10.5403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Quon M. J., Guerre-Millo M., Zarnowski M. J., Butte A. J., Em M., Cushman S. W., Taylor S. I. Tyrosine kinase-deficient mutant human insulin receptors (Met1153-->Ile) overexpressed in transfected rat adipose cells fail to mediate translocation of epitope-tagged GLUT4. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5587–5591. doi: 10.1073/pnas.91.12.5587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Reynet C., Kahn C. R. Rad: a member of the Ras family overexpressed in muscle of type II diabetic humans. Science. 1993 Nov 26;262(5138):1441–1444. doi: 10.1126/science.8248782. [DOI] [PubMed] [Google Scholar]
  44. Robinson L. J., Razzack Z. F., Lawrence J. C., Jr, James D. E. Mitogen-activated protein kinase activation is not sufficient for stimulation of glucose transport or glycogen synthase in 3T3-L1 adipocytes. J Biol Chem. 1993 Dec 15;268(35):26422–26427. [PubMed] [Google Scholar]
  45. Rodriguez-Viciana P., Warne P. H., Dhand R., Vanhaesebroeck B., Gout I., Fry M. J., Waterfield M. D., Downward J. Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 1994 Aug 18;370(6490):527–532. doi: 10.1038/370527a0. [DOI] [PubMed] [Google Scholar]
  46. Schu P. V., Takegawa K., Fry M. J., Stack J. H., Waterfield M. D., Emr S. D. Phosphatidylinositol 3-kinase encoded by yeast VPS34 gene essential for protein sorting. Science. 1993 Apr 2;260(5104):88–91. doi: 10.1126/science.8385367. [DOI] [PubMed] [Google Scholar]
  47. Simpson I. A., Cushman S. W. Hormonal regulation of mammalian glucose transport. Annu Rev Biochem. 1986;55:1059–1089. doi: 10.1146/annurev.bi.55.070186.005211. [DOI] [PubMed] [Google Scholar]
  48. Skolnik E. Y., Batzer A., Li N., Lee C. H., Lowenstein E., Mohammadi M., Margolis B., Schlessinger J. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science. 1993 Jun 25;260(5116):1953–1955. doi: 10.1126/science.8316835. [DOI] [PubMed] [Google Scholar]
  49. Skolnik E. Y., Lee C. H., Batzer A., Vicentini L. M., Zhou M., Daly R., Myers M. J., Jr, Backer J. M., Ullrich A., White M. F. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. EMBO J. 1993 May;12(5):1929–1936. doi: 10.1002/j.1460-2075.1993.tb05842.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Smith R. M., Charron M. J., Shah N., Lodish H. F., Jarett L. Immunoelectron microscopic demonstration of insulin-stimulated translocation of glucose transporters to the plasma membrane of isolated rat adipocytes and masking of the carboxyl-terminal epitope of intracellular GLUT4. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6893–6897. doi: 10.1073/pnas.88.15.6893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Stoyanov B., Volinia S., Hanck T., Rubio I., Loubtchenkov M., Malek D., Stoyanova S., Vanhaesebroeck B., Dhand R., Nürnberg B. Cloning and characterization of a G protein-activated human phosphoinositide-3 kinase. Science. 1995 Aug 4;269(5224):690–693. doi: 10.1126/science.7624799. [DOI] [PubMed] [Google Scholar]
  52. Suzuki K., Kono T. Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc Natl Acad Sci U S A. 1980 May;77(5):2542–2545. doi: 10.1073/pnas.77.5.2542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Szeberényi J., Cai H., Cooper G. M. Effect of a dominant inhibitory Ha-ras mutation on neuronal differentiation of PC12 cells. Mol Cell Biol. 1990 Oct;10(10):5324–5332. doi: 10.1128/mcb.10.10.5324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Ullrich O., Stenmark H., Alexandrov K., Huber L. A., Kaibuchi K., Sasaki T., Takai Y., Zerial M. Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J Biol Chem. 1993 Aug 25;268(24):18143–18150. [PubMed] [Google Scholar]
  55. Vogt B., Mushack J., Seffer E., Häring H. U. The translocation of the glucose transporter sub-types GLUT1 and GLUT4 in isolated fat cells is differently regulated by phorbol esters. Biochem J. 1991 May 1;275(Pt 3):597–600. doi: 10.1042/bj2750597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Volinia S., Dhand R., Vanhaesebroeck B., MacDougall L. K., Stein R., Zvelebil M. J., Domin J., Panaretou C., Waterfield M. D. A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-Vps15p protein sorting system. EMBO J. 1995 Jul 17;14(14):3339–3348. doi: 10.1002/j.1460-2075.1995.tb07340.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Wiese R. J., Mastick C. C., Lazar D. F., Saltiel A. R. Activation of mitogen-activated protein kinase and phosphatidylinositol 3'-kinase is not sufficient for the hormonal stimulation of glucose uptake, lipogenesis, or glycogen synthesis in 3T3-L1 adipocytes. J Biol Chem. 1995 Feb 17;270(7):3442–3446. doi: 10.1074/jbc.270.7.3442. [DOI] [PubMed] [Google Scholar]
  58. Xiao S., Rose D. W., Sasaoka T., Maegawa H., Burke T. R., Jr, Roller P. P., Shoelson S. E., Olefsky J. M. Syp (SH-PTP2) is a positive mediator of growth factor-stimulated mitogenic signal transduction. J Biol Chem. 1994 Aug 19;269(33):21244–21248. [PubMed] [Google Scholar]
  59. Yamamoto M., Marui N., Sakai T., Morii N., Kozaki S., Ikai K., Imamura S., Narumiya S. ADP-ribosylation of the rhoA gene product by botulinum C3 exoenzyme causes Swiss 3T3 cells to accumulate in the G1 phase of the cell cycle. Oncogene. 1993 Jun;8(6):1449–1455. [PubMed] [Google Scholar]
  60. van den Berghe N., Ouwens D. M., Maassen J. A., van Mackelenbergh M. G., Sips H. C., Krans H. M. Activation of the Ras/mitogen-activated protein kinase signaling pathway alone is not sufficient to induce glucose uptake in 3T3-L1 adipocytes. Mol Cell Biol. 1994 Apr;14(4):2372–2377. doi: 10.1128/mcb.14.4.2372. [DOI] [PMC free article] [PubMed] [Google Scholar]

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