ArticlePharmaceutical research2009
Reduced antidiabetic effect of metformin and down-regulation of hepatic Oct1 in rats with ethynylestradiol-induced cholestasis.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Role of metformin in overweight and obese people without diabetes: a systematic review and network meta-analysis.European journal of clinical pharmacology · 2019Pooled it
- The Molecular Mechanisms of Metformin's Action on Blood Lipid Profile in Diabetic Patients.International journal of molecular sciences · 2026Review
- Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.Acta pharmaceutica Sinica. B · 2023Article
- Metabolic Action of Metformin.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology.International journal of molecular sciences · 2020Review
- Anti-inflammatory Property of AMP-activated Protein Kinase.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2020Review
- Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract.Pharmaceutics · 2019Article
- Ursodeoxycholate Restores Biliary Excretion of Methotrexate in Rats with Ethinyl Estradiol Induced-Cholestasis by Restoring Canalicular Mrp2 Expression.International journal of molecular sciences · 2018Article
- Effect of Liver Disease on Hepatic Transporter Expression and Function.Journal of pharmaceutical sciences · 2017Review
- Altered Expression of Transporters, its Potential Mechanisms and Influences in the Liver of Rodent Models Associated with Diabetes Mellitus and Obesity.European journal of drug metabolism and pharmacokinetics · 2016Review
- Role of age-related decrease of renal organic cation transporter 2 in the effect of atenolol on renal excretion of metformin in rats.European journal of drug metabolism and pharmacokinetics · 2015Article
- Small molecule adenosine 5'-monophosphate activated protein kinase (AMPK) modulators and human diseases.Journal of medicinal chemistry · 2015Review
- Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction.PloS one · 2015Article
- Drug disposition alterations in liver disease: extrahepatic effects in cholestasis and nonalcoholic steatohepatitis.Expert opinion on drug metabolism & toxicology · 2014Review
- Genetic polymorphisms of OCT-1 confer susceptibility to severe progression of primary biliary cirrhosis in Japanese patients.Journal of gastroenterology · 2014Article
- AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases.Journal of lipid research · 2012Review
- Endocrine and metabolic regulation of renal drug transporters.Journal of biochemical and molecular toxicology · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the effect of 17alpha-ethynylestradiol (EE)-induced cholestasis on the expression of organic cation transporters (Octs) in the liver and kidney, as well as the pharmacokinetics and pharmacodynamics of metformin in rats.
methodsOcts mRNA and protein expression were determined. The pharmacokinetics and tissue uptake clearance of metformin were determined following iv administration (5 mg/kg). Uptake of metformin, glucagon-mediated glucose production, and AMP-activated protein kinase (AMPK) activation were measured in isolated hepatocytes. The effect of metformin (30 mg/kg) on blood glucose levels was tested using the iv glucose tolerance test (IVGTT).
resultsThe mRNAs of hepatic Oct1, renal Oct1, and Oct2 were decreased by 71.1%, 37.6%, and 94.5%, respectively, by EE cholestasis. The hepatic Oct1 and renal Oct2 proteins were decreased by 30.6% and 60.2%, respectively. The systemic and renal clearance of metformin were decreased. The in vitro hepatocyte uptake of metformin was decreased by 86.4% for V (max). Suppression of glucagon-stimulated glucose production and stimulation of AMPK activation in hepatocytes by metformin were diminished. In addition, metformin did not demonstrate a glucose-lowering effect during IVGTT in EE cholestasis.
conclusionThe antidiabetic effect of metformin may be diminished in diabetic patients with EE cholestasis, due to impaired hepatic uptake of the drug via OCT1.
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Registered trials
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