ArticlePloS one2014
Involvement of increased endogenous asymmetric dimethylarginine in the hepatic endoplasmic reticulum stress of type 2 diabetic rats.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
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- The Molecular Mechanism of Renal Tubulointerstitial Inflammation Promoting Diabetic Nephropathy.International journal of nephrology and renovascular disease · 2023Review
- Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistanceFrontiers in pharmacology · 2022Article
- Pilea umbrosa ameliorate CClEnvironmental health and preventive medicine · 2020Article
- Endogenous asymmetric dimethylarginine accumulation contributes to the suppression of myocardial mitochondrial biogenesis in type 2 diabetic rats.Nutrition & metabolism · 2020Article
- Asymmetric dimethylarginine downregulates sarco/endoplasmic reticulum calcium‑ATPase 3 and induces endoplasmic reticulum stress in human umbilical vein endothelial cells.Molecular medicine reports · 2017Article
- Article
- High-fructose diet is as detrimental as high-fat diet in the induction of insulin resistance and diabetes mediated by hepatic/pancreatic endoplasmic reticulum (ER) stress.Molecular and cellular biochemistry · 2016Article
- MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.Molecular and cellular biochemistry · 2016Article
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6 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
objectiveIncreasing evidence suggested that endoplasmic reticulum (ER) stress contributes to insulin resistance, which plays an important role in the development of type 2 diabetes mellitus (T2DM). Accumulation of endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA), is associated with insulin resistance, T2DM, and diabetic cardiovascular complications, although the mechanisms have not been elucidated. This study was to determine whether elevated endogenous ADMA is involved in hepatic ER stress of type 2 diabetic rats, verify their causal relationship, and elucidate the potential mechanism underlying ADMA induced ER stress in rat hepatocytes.
methodsImmunoglobulin binding protein (Bip) transcription, eukaryotic initiation factor 2α kinase (eIF2α) phosphorylation, X box-binding protein-1 (XBP-1) mRNA splicing and C/EBP homologues protein (CHOP) expression were measured to reflect ER stress. Contents of ADMA and nitrite/nitrate as well as activities or expression of NOS and dimethylarginine dimethylaminohydrolase (DDAH) were detected to show the changes in DDAH/ADMA/NOS/NO pathway. The lipid peroxidation product malondialdehyde content and antioxidant enzyme superoxide dismutase activity were analyzed to evaluate oxidative stress.
resultsER stress was provoked in the liver of type 2 diabetic rats, as expressed by increases of Bip transcription, eIF2α phosphorylation, XBP-1 splicing and CHOP expression, all of which were in parallel with the elevation of serum ADMA, suppression of NO generation, NOS and DDAH activities in the liver. Exposure of hepatocytes to ADMA or hydrogen peroxide also induced ER stress, which was associated with the inhibition of NO production and increase of oxidative stress. Treatment of hepatocytes with antioxidant pyrrolidine dithiocarbamate not only decreased ADMA-induced oxidative stress and inhibition of NO production but also reduced ADMA-triggered ER stress.
conclusionsThese results indicate that increased endogenous ADMA contributes to hepatic ER stress in type 2 diabetic rats, and the mechanism underlying ADMA-induced ER stress may relate to oxidative stress via NOS uncoupling.
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