Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus - PubMed (original) (raw)
Transgenic expression of antioxidant protein thioredoxin in pancreatic beta cells prevents progression of type 2 diabetes mellitus
Mayu Yamamoto et al. Antioxid Redox Signal. 2008 Jan.
Abstract
The authors previously established a transgenic mouse line in the type 1 diabetes model, NOD mouse, in which thioredoxin (TRX), a redox protein, is overexpressed in pancreatic beta cells, and found that TRX overexpression slows the progression of type 1 diabetes. Recent reports on type 2 diabetes suggest that oxidative stress also degrades the function of beta cells. To elucidate whether TRX overexpression can prevent progressive beta cell failure from oxidative stress in type 2 diabetes, the authors transferred the TRX transgene from the NOD mouse onto a mouse model of type 2 diabetes, the db/db mouse. The progression of hyperglycemia and the reduction of body weight gain and insulin content of the db/db mouse were significantly suppressed by the TRX expression. Furthermore, TRX suppressed the reduction of Pdx-1 and MafA expression in the beta cells, which may be one of the cellular mechanisms for protecting beta cells from losing their insulin-secreting capacity. These results showed that TRX can protect beta cells from destruction not only in type 1 but also in type 2 diabetes, and that they provide evidence that oxidative stress plays a crucial role in the deterioration of beta cell function during the progression of type 2 diabetes.
Similar articles
- Pancreatic beta cell-specific expression of thioredoxin, an antioxidative and antiapoptotic protein, prevents autoimmune and streptozotocin-induced diabetes.
Hotta M, Tashiro F, Ikegami H, Niwa H, Ogihara T, Yodoi J, Miyazaki J. Hotta M, et al. J Exp Med. 1998 Oct 19;188(8):1445-51. doi: 10.1084/jem.188.8.1445. J Exp Med. 1998. PMID: 9782121 Free PMC article. - Overexpression of redox-active protein thioredoxin-1 prevents development of chronic pancreatitis in mice.
Ohashi S, Nishio A, Nakamura H, Asada M, Tamaki H, Kawasaki K, Fukui T, Yodoi J, Chiba T. Ohashi S, et al. Antioxid Redox Signal. 2006 Sep-Oct;8(9-10):1835-45. doi: 10.1089/ars.2006.8.1835. Antioxid Redox Signal. 2006. PMID: 16987036 - Pancreatic β-cell glucose toxicity in type 2 diabetes mellitus.
Kaneto H. Kaneto H. Curr Diabetes Rev. 2015;11(1):2-6. doi: 10.2174/1573399811666141216160217. Curr Diabetes Rev. 2015. PMID: 25515340 Review. - Role of oxidative stress in pancreatic beta-cell dysfunction.
Kajimoto Y, Kaneto H. Kajimoto Y, et al. Ann N Y Acad Sci. 2004 Apr;1011:168-76. doi: 10.1007/978-3-662-41088-2_17. Ann N Y Acad Sci. 2004. PMID: 15126294 - Role of PDX-1 and MafA as a potential therapeutic target for diabetes.
Kaneto H, Miyatsuka T, Fujitani Y, Noguchi H, Song KH, Yoon KH, Matsuoka TA. Kaneto H, et al. Diabetes Res Clin Pract. 2007 Sep;77 Suppl 1:S127-37. doi: 10.1016/j.diabres.2007.01.046. Epub 2007 Apr 20. Diabetes Res Clin Pract. 2007. PMID: 17449132 Review.
Cited by
- The Protective Action of Metformin against Pro-Inflammatory Cytokine-Induced Human Islet Cell Damage and the Mechanisms Involved.
Giusti L, Tesi M, Ciregia F, Marselli L, Zallocco L, Suleiman M, De Luca C, Del Guerra S, Zuccarini M, Trerotola M, Eizirik DL, Cnop M, Mazzoni MR, Marchetti P, Lucacchini A, Ronci M. Giusti L, et al. Cells. 2022 Aug 8;11(15):2465. doi: 10.3390/cells11152465. Cells. 2022. PMID: 35954309 Free PMC article. - Mitophagy-mediated adipose inflammation contributes to type 2 diabetes with hepatic insulin resistance.
He F, Huang Y, Song Z, Zhou HJ, Zhang H, Perry RJ, Shulman GI, Min W. He F, et al. J Exp Med. 2021 Mar 1;218(3):e20201416. doi: 10.1084/jem.20201416. J Exp Med. 2021. PMID: 33315085 Free PMC article. - Genetics of type-1 diabetes.
Ikegami H, Noso S. Ikegami H, et al. Diabetol Int. 2024 Sep 2;15(4):688-698. doi: 10.1007/s13340-024-00754-1. eCollection 2024 Oct. Diabetol Int. 2024. PMID: 39469551 Review. - The role of thioredoxin 1 in the mycophenolic acid-induced apoptosis of insulin-producing cells.
Huh KH, Cho Y, Kim BS, Do JH, Park YJ, Joo DJ, Kim MS, Kim YS. Huh KH, et al. Cell Death Dis. 2013 Jul 11;4(7):e721. doi: 10.1038/cddis.2013.247. Cell Death Dis. 2013. PMID: 23846223 Free PMC article. - Preventing p38 MAPK-mediated MafA degradation ameliorates β-cell dysfunction under oxidative stress.
El Khattabi I, Sharma A. El Khattabi I, et al. Mol Endocrinol. 2013 Jul;27(7):1078-90. doi: 10.1210/me.2012-1346. Epub 2013 May 9. Mol Endocrinol. 2013. PMID: 23660596 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous