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Hernandez LF, Buchwald P, Abdulreda MH. Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD Mice. Curr Res Diabetes Obes J. 2018;5(3)
Hernandez, L. F., Buchwald, P., & Abdulreda, M. H. (2018). Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD Mice. Current research in diabetes & obesity journal, 5(3), .
Hernandez, Luis F, et al. "Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD Mice." Current research in diabetes & obesity journal vol. 5,3 (2018).
Hernandez LF, Buchwald P, Abdulreda MH. Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD Mice. Curr Res Diabetes Obes J. 2018 Jan;5(3). Epub 2018 Aug 01. PMID: 29450408; PMCID: PMC5810145.
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Curr Res Diabetes Obes J. 2018 Jan;5(3). Epub 2018 Aug 01.

Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD Mice.

Current research in diabetes & obesity journal

Luis F Hernandez, Peter Buchwald, Midhat H Abdulreda

Affiliations

  1. Diabetes Research Institute, University of Miami Miller School of Medicine, USA.
  2. Department of Molecular & Cellular Pharmacology, University of Miami Miller School of Medicine, USA.
  3. Department of Surgery, University of Miami Miller School of Medicine, USA.

PMID: 29450408 PMCID: PMC5810145

Abstract

Metabolism of the amino acid L-arginine is implicated in many physiological and pathophysiological processes including autoimmune conditions such as type 1 diabetes (T1D). Alternate arginine metabolism through the citrulline-nitric oxide (NO) or the ornithine pathways can lead to proinflammatory or immune regulatory effects, respectively. In this report, we blocked the arginine-ornithine metabolic pathway by inhibiting the enzyme arginase-1 with Nω-hydroxy-nor-arginine (nor-NOHA) to make arginine more available to the alternate citrulline pathway for augmented NO production and increased incidence of autoimmune T1D in female non-obese diabetic (NOD) mice. Unexpectedly, mice receiving nor-NOHA did not develop diabetes although increased NO production is proinflammatory and expected to increase diabetes incidence. These results warrant further studies of the mechanism of action of nor-NOHA, and highlight its potential as a therapeutic agent for the treatment or prevention of T1D.

Keywords: Arginine; Incidence rate; Inflammation; Macrophages; Metabolism; NOD; Nitric oxide; Ornithine; T1D; nor-NOHA

References

  1. Methods Mol Biol. 2007;380:285-311 - PubMed
  2. Immunity. 2005 Aug;23(2):115-26 - PubMed
  3. Nat Rev Endocrinol. 2015 May;11(5):308-14 - PubMed
  4. IUBMB Life. 2015 Aug;67(8):634-44 - PubMed
  5. Cell Death Differ. 2003 Aug;10(8):864-9 - PubMed
  6. J Biol Chem. 2013 Dec 20;288(51):36226-35 - PubMed
  7. Nat Med. 2007 Oct;13(10):1176-84 - PubMed
  8. Immunity. 1997 Dec;7(6):727-38 - PubMed
  9. Curr Pharm Des. 2014;20(2):284-92 - PubMed
  10. Curr Protoc Immunol. 2001 May;Chapter 15:Unit 15.9 - PubMed
  11. Nat Rev Immunol. 2004 Dec;4(12 ):989-97 - PubMed
  12. Amino Acids. 2014 Mar;46(3):633-42 - PubMed
  13. Inflammation. 2013 Feb;36(1):141-51 - PubMed
  14. Biochem Biophys Res Commun. 2015 Aug 28;464(3):840-7 - PubMed
  15. J Immunol. 2010 Jun 15;184(12):6882-90 - PubMed
  16. Biochim Biophys Acta. 1999 May 5;1411(2-3):401-14 - PubMed
  17. J Proteome Res. 2017 Oct 6;16(10 ):3873-3890 - PubMed
  18. Nat Med. 1997 Oct;3(10):1089-95 - PubMed
  19. PLoS One. 2009 Sep 21;4(9):e7059 - PubMed
  20. Curr Opin Rheumatol. 2015 May;27(3):262-7 - PubMed
  21. Nitric Oxide. 1999 Dec;3(6):427-38 - PubMed
  22. Proc Natl Acad Sci U S A. 2016 Feb 2;113(5):1191-6 - PubMed
  23. FEBS Lett. 1998 Aug 14;433(1-2):125-31 - PubMed
  24. Arthritis Res Ther. 2012 May 30;14(3):R130 - PubMed
  25. Math Biosci. 2007 Jan;205(1):108-36 - PubMed
  26. Annu Rev Immunol. 2005;23:447-85 - PubMed
  27. J Clin Invest. 2010 Jun;120(6):2156-70 - PubMed

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