Effect of Arginase-1 Inhibition on the Incidence of Autoimmune Diabetes in NOD Mice.
Curr Res Diabetes Obes J
; 5(3)2018 Jan.
Article
em En
| MEDLINE
| ID: mdl-29450408
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.
Texto completo:
1
Base de dados:
MEDLINE
Tipo de estudo:
Incidence_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Curr Res Diabetes Obes J
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos