ArticlePloS one2013
FXR agonist INT-747 upregulates DDAH expression and enhances insulin sensitivity in high-salt fed Dahl rats.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Genomics link obesity and type 2 diabetes to Alzheimer's disease to unveil novel biological insights.medRxiv : the preprint server for health sciences · 2026Article
- Role of FXR in Renal Physiology and Kidney Diseases.International journal of molecular sciences · 2023Review
- Psyllium Fiber Protects Against Colitis Via Activation of Bile Acid Sensor Farnesoid X Receptor.Cellular and molecular gastroenterology and hepatology · 2023Article
- Bile acid receptors and renal regulation of water homeostasis.Frontiers in physiology · 2023Review
- DDAH1 Protects against Acetaminophen-Induced Liver Hepatoxicity in Mice.Antioxidants (Basel, Switzerland) · 2022Article
- Farnesoid X receptor signaling activates the hepatic X-box binding protein 1 pathway in vitro and in mice.Hepatology (Baltimore, Md.) · 2018Article
- Article
- Asymmetric Dimethylarginine and Hepatic Encephalopathy: Cause, Effect or Association?Neurochemical research · 2017Review
- Farnesoid X Receptor Activation Attenuates Intestinal Ischemia Reperfusion Injury in Rats.PloS one · 2017Article
- Inhibitors of the Hydrolytic Enzyme Dimethylarginine Dimethylaminohydrolase (DDAH): Discovery, Synthesis and Development.Molecules (Basel, Switzerland) · 2016Review
- Modulating DDAH/NOS Pathway to Discover Vasoprotective Insulin Sensitizers.Journal of diabetes research · 2016Review
- Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension.Journal of hepatology · 2015Article
- Endogenous Asymmetric Dimethylarginine Pathway in High Altitude Adapted Yaks.BioMed research international · 2015Article
- Coordinated Actions of FXR and LXR in Metabolism: From Pathogenesis to Pharmacological Targets for Type 2 Diabetes.International journal of endocrinology · 2014Review
- Biological functional relevance of asymmetric dimethylarginine (ADMA) in cardiovascular disease.International journal of molecular sciences · 2013Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsGenetic 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. METHODS AND
resultsIn 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.
conclusionOur study may provide the basis for a new therapeutic approach for IR by modulating DDAH expression and/or activity using small molecules.
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Registered trials
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