Display options
Cite
Beaton N, Rudigier C, Moest H, et al. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling. Mol Metab. 2015;4(11):795-810doi: 10.1016/j.molmet.2015.08.003.
Beaton, N., Rudigier, C., Moest, H., Müller, S., Mrosek, N., Röder, E., Rudofsky, G., Rülicke, T., Ukropec, J., Ukropcova, B., Augustin, R., Neubauer, H., & Wolfrum, C. (2015). TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling. Molecular metabolism, 4(11), 795-810. https://doi.org/10.1016/j.molmet.2015.08.003
Beaton, Nigel, et al. "TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling." Molecular metabolism vol. 4,11 (2015): 795-810. doi: https://doi.org/10.1016/j.molmet.2015.08.003
Beaton N, Rudigier C, Moest H, Müller S, Mrosek N, Röder E, Rudofsky G, Rülicke T, Ukropec J, Ukropcova B, Augustin R, Neubauer H, Wolfrum C. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling. Mol Metab. 2015 Aug 28;4(11):795-810. doi: 10.1016/j.molmet.2015.08.003. eCollection 2015 Nov. PMID: 26629404; PMCID: PMC4632119.
Copy Download .nbib Format: NLM
Share it on

Mol Metab. 2015 Aug 28;4(11):795-810. doi: 10.1016/j.molmet.2015.08.003. eCollection 2015 Nov.

TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling.

Molecular metabolism

Nigel Beaton, Carla Rudigier, Hansjörg Moest, Sebastian Müller, Nadja Mrosek, Eva Röder, Gottfried Rudofsky, Thomas Rülicke, Jozef Ukropec, Barbara Ukropcova, Robert Augustin, Heike Neubauer, Christian Wolfrum

Affiliations

  1. Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, Switzerland.
  2. Department of Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany.
  3. Institute of Laboratory Animal Science, Vetmeduni, Vienna, Austria.
  4. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia.
  5. Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava, Slovakia ; Institute of Pathophysiology, School of Medicine, Comenius University, Bratislava, Slovakia.
  6. CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH&Co. KG, Biberach a.d. Riss, Germany ; Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH&CoKG, Biberach a.d. Riss, Germany.
  7. CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH&Co. KG, Biberach a.d. Riss, Germany.

PMID: 26629404 PMCID: PMC4632119 DOI: 10.1016/j.molmet.2015.08.003

Abstract

OBJECTIVE: Failure to properly dispose of glucose in response to insulin is a serious health problem, occurring during obesity and is associated with type 2 diabetes development. Insulin-stimulated glucose uptake is facilitated by the translocation and plasma membrane fusion of vesicles containing glucose transporter 4 (GLUT4), the rate-limiting step of post-prandial glucose disposal.

METHODS: We analyzed the role of Tusc5 in the regulation of insulin-stimulated Glut4-mediated glucose uptake in vitro and in vivo. Furthermore, we measured Tusc5 expression in two patient cohorts.

RESULTS: Herein, we report that TUSC5 controls insulin-stimulated glucose uptake in adipocytes, in vitro and in vivo. TUSC5 facilitates the proper recycling of GLUT4 and other key trafficking proteins during prolonged insulin stimulation, thereby enabling proper protein localization and complete vesicle formation, processes that ultimately enable insulin-stimulated glucose uptake. Tusc5 knockout mice exhibit impaired glucose disposal and TUSC5 expression is predictive of glucose tolerance in obese individuals, independent of body weight. Furthermore, we show that TUSC5 is a PPARγ target and in its absence the anti-diabetic effects of TZDs are significantly blunted.

CONCLUSIONS: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

Keywords: Glucose uptake; Insulin resistance; Obesity; Type 2 diabetes

References

  1. J Clin Invest. 1988 May;81(5):1563-71 - PubMed
  2. Mol Cell Endocrinol. 2007 Sep 30;276(1-2):24-35 - PubMed
  3. J Cell Biol. 2008 Jan 28;180(2):375-87 - PubMed
  4. Mol Cell Proteomics. 2007 Jun;6(6):1007-17 - PubMed
  5. Mol Cell Biol. 2004 Jul;24(14):6456-66 - PubMed
  6. Acta Physiol (Oxf). 2008 Jan;192(1):89-101 - PubMed
  7. Methods Mol Biol. 2001;155:77-82 - PubMed
  8. J Biol Chem. 1999 Dec 24;274(52):37357-61 - PubMed
  9. Traffic. 2011 Jun;12(6):657-64 - PubMed
  10. Mol Cell Endocrinol. 2007 Jan 15;263(1-2):38-45 - PubMed
  11. J Biol Chem. 1995 Oct 6;270(40):23612-8 - PubMed
  12. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80 - PubMed
  13. Proteomics. 2006 Dec;6(23):6250-62 - PubMed
  14. Nature. 1995 Sep 14;377(6545):151-5 - PubMed
  15. EMBO J. 2006 Dec 13;25(24):5648-58 - PubMed
  16. J Biol Chem. 2007 Mar 23;282(12):9008-16 - PubMed
  17. Horm Metab Res. 2011 May;43(5):343-8 - PubMed
  18. EMBO Mol Med. 2011 Nov;3(11):637-51 - PubMed
  19. FEBS Lett. 1998 May 8;427(2):193-7 - PubMed
  20. Nature. 2006 Dec 14;444(7121):881-7 - PubMed
  21. J Biol Chem. 2000 Nov 17;275(46):36263-8 - PubMed
  22. Mol Cell Proteomics. 2005 Aug;4(8):1095-106 - PubMed
  23. Diabetologia. 2000 Oct;43(10 ):1273-81 - PubMed
  24. J Biol Chem. 2003 Mar 21;278(12):10683-90 - PubMed
  25. Cell Metab. 2013 Apr 2;17(4):575-85 - PubMed
  26. J Cell Biol. 2011 May 16;193(4):643-53 - PubMed
  27. J Biol Chem. 2008 Jan 4;283(1):311-23 - PubMed
  28. Mol Biol Cell. 2000 Dec;11(12):4079-91 - PubMed
  29. Cell Metab. 2007 Apr;5(4):237-52 - PubMed
  30. Mol Biol Cell. 1999 Nov;10 (11):3675-88 - PubMed
  31. Am J Physiol Endocrinol Metab. 2005 Oct;289(4):E551-61 - PubMed
  32. Nature. 2003 Oct 16;425(6959):727-33 - PubMed
  33. Mol Metab. 2013 Mar 16;2(3):314-23 - PubMed
  34. Biochem Biophys Res Commun. 2006 Aug 25;347(2):433-8 - PubMed
  35. Mol Syst Biol. 2009;5:260 - PubMed
  36. J Biol Chem. 2008 Oct 31;283(44):30311-21 - PubMed
  37. J Clin Invest. 1998 Jun 1;101(11):2377-86 - PubMed
  38. Mol Biol Cell. 2008 Aug;19(8):3477-87 - PubMed
  39. Biochem Biophys Res Commun. 2007 Aug 17;360(1):139-45 - PubMed
  40. Nat Med. 1997 Oct;3(10):1096-101 - PubMed
  41. Dev Cell. 2005 Jul;9(1):99-108 - PubMed
  42. J Biol Chem. 2010 Jan 1;285(1):104-14 - PubMed
  43. Annu Rev Biochem. 2012;81:507-32 - PubMed
  44. Mol Biol Cell. 2003 Jul;14(7):2946-58 - PubMed
  45. Biochemistry. 2011 Apr 19;50(15):3048-61 - PubMed
  46. J Cell Sci. 2000 Nov;113 ( Pt 22):4065-76 - PubMed
  47. J Biol Chem. 1997 Sep 12;272(37):23323-7 - PubMed
  48. Diabetes. 1996 Jan;45(1):23-7 - PubMed
  49. Nature. 2006 Dec 14;444(7121):840-6 - PubMed
  50. PLoS One. 2013 Jul 16;8(7):e68516 - PubMed
  51. J Biol Chem. 2015 Sep 25;290(39):23528-42 - PubMed
  52. J Cell Biol. 2002 Feb 18;156(4):653-64 - PubMed
  53. J Biol Chem. 2003 Apr 25;278(17 ):14599-602 - PubMed
  54. Diabetes Obes Metab. 2013 Nov;15(11):967-77 - PubMed
  55. Nature. 2001 Feb 8;409(6821):729-33 - PubMed
  56. J Clin Invest. 1995 Jan;95(1):429-32 - PubMed
  57. J Biol Chem. 1993 Jul 5;268(19):14523-6 - PubMed
  58. PPAR Res. 2009;2009:867678 - PubMed
  59. Biochem Biophys Res Commun. 2010 Jan 15;391(3):1336-41 - PubMed
  60. Traffic. 2011 Jun;12(6):665-71 - PubMed
  61. Cell. 2008 Dec 26;135(7):1175-87 - PubMed
  62. Traffic. 2008 Jul;9(7):1173-90 - PubMed
  63. J Biol Chem. 2002 Mar 15;277(11):9133-8 - PubMed
  64. Endocrinology. 1997 Apr;138(4):1604-11 - PubMed
  65. J Clin Endocrinol Metab. 2008 Jun;93(6):2255-62 - PubMed
  66. Mol Biol Cell. 2000 Jul;11(7):2403-17 - PubMed
  67. J Biol Chem. 2005 Nov 11;280(45):37803-13 - PubMed
  68. Mol Biol Cell. 2003 Mar;14(3):973-86 - PubMed
  69. Nat Rev Mol Cell Biol. 2012 May 23;13(6):383-96 - PubMed
  70. Nat Med. 2000 Aug;6(8):924-8 - PubMed
  71. J Biol Chem. 2012 Feb 24;287(9):6421-30 - PubMed

Publication Types