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Christine Johnson, MD

  • Christine Luk Chiang Johnson

Especialidades médicas y/o especialidades quirúrgicas

Neonatal-Perinatal Medicine

Trabajo y educación

Educación

LAC+USC Medical Center Internal Medicine Residency, Los Angeles, CA, 05/2007

Primeros años de residencia

University of Minnesota, Minneapolis, MN, 06/2008

Últimos años de residencia

University of Minnesota, Minneapolis, MN, 06/2010

Subespecialidad

Stanford University, Palo Alto, CA, 6/2013

Certificado(s) de especialidad

Neonatal-Perinatal Medicine, American Board of Pediatrics

Pediatrics, American Board of Pediatrics

Servicios

Neonatología

Todo Publicaciones

FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. PloS one Ghebremariam, Y. T., Yamada, K., Lee, J. C., Johnson, C. L., Atzler, D., Anderssohn, M., Agrawal, R., Higgins, J. P., Patterson, A. J., Bger, R. H., Cooke, J. P. 2013; 8 (4)

Abstract

Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR)-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity.In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS). Our data indicates that high salt (HS) diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls.Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.

View details for DOI 10.1371/journal.pone.0060653

View details for PubMedID 23593273

View details for PubMedCentralID PMC3617194

FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats. PloS one Ghebremariam, Y. T., Yamada, K., Lee, J. C., Johnson, C. L., Atzler, D., Anderssohn, M., Agrawal, R., Higgins, J. P., Patterson, A. J., Bger, R. H., Cooke, J. P. 2013; 8 (4): e60653

Abstract

Genetic and pharmacological studies have shown that impairment of the nitric oxide (NO) synthase (NOS) pathway is associated with hypertension and insulin-resistance (IR). In addition, inhibition of NOS by the endogenous inhibitor, asymmetric dimethylarginine (ADMA), may also result in hypertension and IR. On the other hand, overexpression of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that metabolizes ADMA, in mice is associated with lower ADMA, increased NO and enhanced insulin sensitivity. Since DDAH carries a farnesoid X receptor (FXR)-responsive element, we aimed to upregulate its expression by an FXR-agonist, INT-747, and evaluate its effect on blood pressure and insulin sensitivity.In this study, we evaluated the in vivo effect of INT-747 on tissue DDAH expression and insulin sensitivity in the Dahl rat model of salt-sensitive hypertension and IR (Dahl-SS). Our data indicates that high salt (HS) diet significantly increased systemic blood pressure. In addition, HS diet downregulated tissue DDAH expression while INT-747 protected the loss in DDAH expression and enhanced insulin sensitivity compared to vehicle controls.Our study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.

View details for DOI 10.1371/journal.pone.0060653

View details for PubMedID 23593273

View details for PubMedCentralID PMC3617194