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Curr Res Diabetes Obes J. 2018 Jan;5(3). pii: 555661. Epub 2018 Aug 1.

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

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


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.


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


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