Ste 315
Palo Alto, CA 94304
Teléfono: (650) 940-7163
Christine Johnson, MD
- Clinical Assistant Professor
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 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 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
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