Table of Contents Author Guidelines Submit a Manuscript
Journal of Diabetes Research
Volume 2013, Article ID 193461, 6 pages
http://dx.doi.org/10.1155/2013/193461
Review Article

Endoplasmic Reticulum Is at the Crossroads of Autophagy, Inflammation, and Apoptosis Signaling Pathways and Participates in the Pathogenesis of Diabetes Mellitus

1Department of Pathophysiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, China
2Department of Pathology, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China
3Institute of Hypoxia Research, School of Basic Medical Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China

Received 1 April 2013; Accepted 8 May 2013

Academic Editor: Jian Xiao

Copyright © 2013 Jing Su et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Kitada, S. Kume, A. Takeda-Watanabe et al., “Sirtuins and renal diseases: relationship with aging and diabetic nephropathy,” Clinical Science, vol. 124, no. 3, pp. 153–164, 2013. View at Google Scholar
  2. E. Mannucci, M. Monami, C. Lamanna et al., “Post-prandial glucose and diabetic complications: systematic review of observational studies,” Acta Diabetologica, vol. 49, no. 4, pp. 307–314, 2012. View at Google Scholar
  3. H. Brody, “Diabetes,” Nature, vol. 485, no. 7398, p. S1, 2012. View at Google Scholar
  4. M. H. Smith, H. L. Ploegh, and J. S. Weissman, “Road to ruin: targeting proteins for degradation in the endoplasmic reticulum,” Science, vol. 334, no. 6059, pp. 1086–1090, 2011. View at Google Scholar
  5. G. S. Hotamisligil, “Endoplasmic reticulum stress and the inflammatory basis of metabolic disease,” Cell, vol. 140, no. 6, pp. 900–917, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Balasubramanyam, L. P. Singh, and S. Rangasamy, “Molecular intricacies and the role of ER stress in diabetes,” Experimental Diabetes Research, vol. 2012, Article ID 958169, 2 pages, 2012. View at Google Scholar
  7. B. O'Sullivan-Murphy and F. Urano, “ER stress as a trigger for beta-cell dysfunction and autoimmunity in type 1 diabetes,” Diabetes, vol. 61, no. 4, pp. 780–781, 2012. View at Google Scholar
  8. D. Ron and P. Walter, “Signal integration in the endoplasmic reticulum unfolded protein response,” Nature Reviews Molecular Cell Biology, vol. 8, no. 7, pp. 519–529, 2007. View at Publisher · View at Google Scholar · View at Scopus
  9. D. R. Beriault and G. H. Werstuck, “The role of glucosamine-induced ER stress in diabetic atherogenesis,” Experimental Diabetes Research, vol. 2012, Article ID 187018, 11 pages, 2012. View at Publisher · View at Google Scholar
  10. A. Bertolotti, Y. Zhang, L. M. Hendershot, H. P. Harding, and D. Ron, “Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response,” Nature Cell Biology, vol. 2, no. 6, pp. 326–332, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. X. Chen, J. Shen, and R. Prywes, “The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the er to the Golgi,” Journal of Biological Chemistry, vol. 277, no. 15, pp. 13045–13052, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. S. Nadanaka, T. Okada, H. Yoshida, and K. Mori, “Role of disulfide bridges formed in the luminal domain of ATF6 in sensing endoplasmic reticulum stress,” Molecular and Cellular Biology, vol. 27, no. 3, pp. 1027–1043, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Y. Hampton, “ER stress response: getting the UPR hand on misfolded proteins,” Current Biology, vol. 10, no. 14, pp. R518–R521, 2000. View at Publisher · View at Google Scholar · View at Scopus
  14. G. Jing, J. J. Wang, and S. X. Zhang, “ER stress and apoptosis: a new mechanism for retinal cell death,” Experimental Diabetes Research, vol. 2012, Article ID 589589, 11 pages, 2012. View at Publisher · View at Google Scholar
  15. A. Kaser, A. H. Lee, A. Franke et al., “XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease,” Cell, vol. 134, no. 5, pp. 743–756, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. T. Rzymski, A. Petry, D. Kracun et al., “The unfolded protein response controls induction and activation of ADAM17/TACE by severe hypoxia and ER stress,” Oncogene, vol. 31, no. 31, pp. 3621–3634, 2012. View at Google Scholar
  17. K. Zhang, “Integration of ER stress, oxidative stress and the inflammatory response in health and disease,” International Journal of Clinical and Experimental Medicine, vol. 3, no. 1, pp. 33–40, 2010. View at Google Scholar
  18. T. Yorimitsu and D. J. Klionsky, “Autophagy: molecular machinery for self-eating,” Cell Death and Differentiation, vol. 12, no. 2, pp. 1542–1552, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. N. Mizushima, B. Levine, A. M. Cuervo, and D. J. Klionsky, “Autophagy fights disease through cellular self-digestion,” Nature, vol. 451, no. 7182, pp. 1069–1075, 2008. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Kroemer, G. Mariño, and B. Levine, “Autophagy and the integrated stress response,” Molecular Cell, vol. 40, no. 2, pp. 280–293, 2010. View at Publisher · View at Google Scholar · View at Scopus
  21. J. J. Yin, Y. B. Li, Y. Wang et al., “The role of autophagy in endoplasmic reticulum stress-induced pancreatic beta cell death,” Autophagy, vol. 8, no. 2, pp. 158–164, 2012. View at Google Scholar
  22. T. Yorimitsu and D. J. Klionsky, “Eating the endoplasmic reticulum: quality control by autophagy,” Trends in Cell Biology, vol. 17, no. 6, pp. 279–285, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. D. C. Rubinsztein, “The roles of intracellular protein-degradation pathways in neurodegeneration,” Nature, vol. 443, no. 7113, pp. 780–786, 2006. View at Publisher · View at Google Scholar · View at Scopus
  24. Y. Nishida, S. Arakawa, K. Fujitani et al., “Discovery of Atg5/Atg7-independent alternative macroautophagy,” Nature, vol. 461, no. 7264, pp. 654–658, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. Y. Tanaka, S. Kume, M. Kitada et al., “Autophagy as a therapeutic target in diabetic nephropathy,” Experimental Diabetes Research, vol. 2012, Article ID 628978, 12 pages, 2012. View at Publisher · View at Google Scholar
  26. C. Ebato, T. Uchida, M. Arakawa et al., “Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet,” Cell Metabolism, vol. 8, no. 4, pp. 325–332, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. H. S. Jung, K. W. Chung, J. Won Kim et al., “Loss of autophagy diminishes pancreatic β cell mass and function with resultant hyperglycemia,” Cell Metabolism, vol. 8, no. 4, pp. 318–324, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Okada, T. Yanagawa, E. Warabi et al., “The α-glucosidase inhibitor acarbose prevents obesity and simple steatosis in sequestosome 1/A170/p62 deficient mice,” Hepatology Research, vol. 39, no. 5, pp. 490–500, 2009. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Geetha, N. Vishwaprakash, M. Sycheva et al., “Sequestosome 1/p62: across diseases,” Biomarkers, vol. 17, no. 2, pp. 99–103, 2012. View at Google Scholar
  30. P. E. Rautou, A. Mansouri, D. Lebrec, F. Durand, D. Valla, and R. Moreau, “Autophagy in liver diseases,” Journal of Hepatology, vol. 53, no. 6, pp. 1123–1134, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Y. Chung, B. Sung, K. J. Jung, Y. Zou, and B. P. Yu, “The molecular inflammatory process in aging,” Antioxidants and Redox Signaling, vol. 8, no. 3-4, pp. 572–581, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. J. F. Navarro-González, C. Mora-Fernández, M. M. De Fuentes, and J. García-Pérez, “Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy,” Nature Reviews Nephrology, vol. 7, no. 6, pp. 327–340, 2011. View at Publisher · View at Google Scholar · View at Scopus
  33. P. Hu, Z. Han, A. D. Couvillon, R. J. Kaufman, and J. H. Exton, “Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1α-mediated NF-κB activation and down-regulation of TRAF2 expression,” Molecular and Cellular Biology, vol. 26, no. 8, pp. 3071–3084, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. X. D. Liu, S. Ko, Y. Xu et al., “Transient aggregation of ubiquitinated proteins is a cytosolic unfolded protein response to inflammation and endoplasmic reticulum stress,” The Journal of Biological Chemistry, vol. 287, no. 23, pp. 19687–19698, 2012. View at Google Scholar
  35. G. S. Hotamisligil, N. S. Shargill, and B. M. Spiegelman, “Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance,” Science, vol. 259, no. 5091, pp. 87–91, 1993. View at Google Scholar · View at Scopus
  36. J. Hirosumi, G. Tuncman, L. Chang et al., “A central, role for JNK in obesity and insulin resistance,” Nature, vol. 420, no. 6913, pp. 333–336, 2002. View at Publisher · View at Google Scholar · View at Scopus
  37. G. Tuncman, J. Hirosumi, G. Solinas, L. Chang, M. Karin, and G. S. Hotamisligil, “Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 28, pp. 10741–10746, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. S. N. Vallerie, M. Furuhashi, R. Fucho, and G. S. Hotamisligil, “A predominant role for parenchymal c-Jun amino terminal kinase (JNK) in the regulation of systemic insulin sensitivity,” PLoS ONE, vol. 3, no. 9, article e3151, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. S. E. Shoelson, J. Lee, and A. B. Goldfine, “Inflammation and insulin resistance,” Journal of Clinical Investigation, vol. 116, no. 7, pp. 1793–1801, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. H. Yamazaki, N. Hiramatsu, K. Hayakawa et al., “Activation of the Akt-NF-κB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response,” Journal of Immunology, vol. 183, no. 2, pp. 1480–1487, 2009. View at Publisher · View at Google Scholar · View at Scopus
  41. I. Ben Mosbah, I. Alfany-Fernández, C. Martel et al., “Endoplasmic reticulum stress inhibition protects steatotic and non-steatotic livers in partial hepatectomy under ischemia-reperfusion,” Cell Death and Disease, vol. 1, no. 7, article no. e52, 2010. View at Publisher · View at Google Scholar · View at Scopus
  42. G. S. Hotamisligil, “Inflammation and metabolic disorders,” Nature, vol. 444, no. 7121, pp. 860–867, 2006. View at Publisher · View at Google Scholar · View at Scopus
  43. V. I. Alexaki, G. Notas, V. Pelekanou et al., “Adipocytes as immune cells: differential expression of TWEAK, BAFF, and APRIL and their receptors (Fn14, BAFF-R, TACI, and BCMA) at different stages of normal and pathological adipose tissue development,” Journal of Immunology, vol. 183, no. 9, pp. 5948–5956, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. M. Feuerer, Y. Shen, D. R. Littman, C. Benoist, and D. Mathis, “How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets,” Immunity, vol. 31, no. 4, pp. 654–664, 2009. View at Publisher · View at Google Scholar · View at Scopus
  45. N. Kawasaki, R. Asada, A. Saito et al., “Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue,” Scientific Reports, vol. 2, article 799, 2012. View at Google Scholar
  46. J. Zhong, X. Rao, J. F. Xu et al., “The role of endoplasmic reticulum stress in autoimmune-mediated beta-cell destruction in type 1 diabetes,” Experimental Diabetes Research, vol. 2012, Article ID 238980, 12 pages, 2012. View at Publisher · View at Google Scholar
  47. I. Mothe-Satney, C. Filloux, H. Amghar et al., “Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin resistance in mice,” Diabetes, vol. 61, no. 9, pp. 2311–2319, 2012. View at Google Scholar
  48. S. Gupta, D. E. Read, A. Deepti et al., “Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis,” Cell Death and Disease, vol. 3, article e333, 2012. View at Google Scholar
  49. R. V. Rao, H. M. Ellerby, and D. E. Bredesen, “Coupling endoplasmic reticulum stress to the cell death program,” Cell Death and Differentiation, vol. 11, no. 4, pp. 372–380, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Kaneko, Y. Niinuma, and Y. Nomura, “Activation signal of nuclear factor-κB in response to endoplasmic reticulum stress is transduced via IRE1 and tumor necrosis factor receptor-associated factor 2,” Biological and Pharmaceutical Bulletin, vol. 26, no. 7, pp. 931–935, 2003. View at Google Scholar · View at Scopus
  51. J. H. Lin, H. Li, D. Yasumura et al., “IRE1 signaling affects cell fate during the unfolded protein response,” Science, vol. 318, no. 5852, pp. 944–949, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Hetz, P. Bernasconi, J. Fisher et al., “Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1α,” Science, vol. 312, no. 5773, pp. 572–576, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. D. Han, A. G. Lerner, L. Vande Walle et al., “IRE1α kinase activation modes control alternate endoribonuclease outputs to determine divergent cell fates,” Cell, vol. 138, no. 3, pp. 562–575, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. U. Özcan, Q. Cao, E. Yilmaz et al., “Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes,” Science, vol. 306, no. 5695, pp. 457–461, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. K. Ozawa, M. Miyazaki, M. Matsuhisa et al., “The endoplasmic reticuluin chaperone improves insulin resistance in type 2 diabetes,” Diabetes, vol. 54, no. 3, pp. 657–663, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. B. Basha, S. M. Samuel, C. R. Triggle et al., “Endothelial dysfunction in diabetes mellitus: possible involvement of endoplasmic reticulum stress?” Experimental Diabetes Research, vol. 2012, Article ID 481840, 14 pages, 2012. View at Publisher · View at Google Scholar
  57. Y. Nakatani, H. Kaneto, D. Kawamori et al., “Involvement of endoplasmic reticulum stress in insulin resistance and diabetes,” Journal of Biological Chemistry, vol. 280, no. 1, pp. 847–851, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. H. L. Kammoun, H. Chabanon, I. Hainault et al., “GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice,” Journal of Clinical Investigation, vol. 119, no. 5, pp. 1201–1215, 2009. View at Publisher · View at Google Scholar · View at Scopus
  59. D. Scheuner, B. Song, E. McEwen et al., “Translational control is required for the unfolded protein response and in vivo glucose homeostasis,” Molecular Cell, vol. 7, no. 6, pp. 1165–1176, 2001. View at Publisher · View at Google Scholar · View at Scopus
  60. H. P. Harding, H. Zeng, Y. Zhang et al., “Diabetes mellitus and exocrine pancreatic dysfunction in Perk-/- mice reveals a role for translational control in secretory cell survival,” Molecular Cell, vol. 7, no. 6, pp. 1153–1163, 2001. View at Publisher · View at Google Scholar · View at Scopus
  61. S. H. Back, D. Scheuner, J. Han et al., “Translation attenuation through eIF2α phosphorylation prevents oxidative stress and maintains the differentiated state in β cells,” Cell Metabolism, vol. 10, no. 1, pp. 13–26, 2009. View at Publisher · View at Google Scholar · View at Scopus
  62. W. C. Ladiges, S. E. Knoblaugh, J. F. Morton et al., “Pancreatic β-cell failure and diabetes in mice with a deletion mutation of the endoplasmic reticulum molecular chaperone gene P58IPK,” Diabetes, vol. 54, no. 4, pp. 1074–1081, 2005. View at Publisher · View at Google Scholar · View at Scopus
  63. P. Zhang, B. McGrath, S. Li et al., “The PERK eukaryotic initiation factor 2α kinase is required for the development of the skeletal system, postnatal growth, and the function and viability of the pancreas,” Molecular and Cellular Biology, vol. 22, no. 11, pp. 3864–3874, 2002. View at Publisher · View at Google Scholar · View at Scopus
  64. S. G. Fonseca, M. Fukuma, K. L. Lipson et al., “WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pacreatic β-cells,” Journal of Biological Chemistry, vol. 280, no. 47, pp. 39609–39615, 2005. View at Publisher · View at Google Scholar · View at Scopus
  65. U. Özcan, E. Yilmaz, L. Özcan et al., “Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes,” Science, vol. 313, no. 5790, pp. 1137–1140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  66. T. Ota, C. Gayet, and H. N. Ginsberg, “Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents,” Journal of Clinical Investigation, vol. 118, no. 1, pp. 316–332, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Boyce, K. F. Bryant, C. Jousse et al., “A selective inhibitor of elF2α dephosphorylation protects cells from ER stress,” Science, vol. 307, no. 5711, pp. 935–939, 2005. View at Publisher · View at Google Scholar · View at Scopus
  68. K. L. Lipson, S. G. Fonseca, S. Ishigaki et al., “Regulation of insulin biosynthesis in pancreatic beta cells by an endoplasmic reticulum-resident protein kinase IRE1,” Cell Metabolism, vol. 4, no. 3, pp. 245–254, 2006. View at Publisher · View at Google Scholar · View at Scopus
  69. C. K. Tsang, H. Qi, L. F. Liu, and X. F. S. Zheng, “Targeting mammalian target of rapamycin (mTOR) for health and diseases,” Drug Discovery Today, vol. 12, no. 3-4, pp. 112–124, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. B. B. Zhang, G. Zhou, and C. Li, “AMPK: an emerging drug target for diabetes and the metabolic syndrome,” Cell Metabolism, vol. 9, no. 5, pp. 407–416, 2009. View at Publisher · View at Google Scholar · View at Scopus