ArticleBMJ open diabetes research & care2014
Statins impair glucose uptake in human cells.
Article in BMJ open diabetes research & care, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
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- Induced pluripotent stem cell-derived cells model brain microvascular endothelial cell glucose metabolism.Fluids and barriers of the CNS · 2022Article
- Macrophage acetyl-CoA carboxylase regulates acute inflammation through control of glucose and lipid metabolism.Science advances · 2022Article
- New onset diabetes mellitus and cardiovascular events in Korean patients with acute myocardial infarction receiving high-intensity statins.BMC pharmacology & toxicology · 2021Article
- Simvastatin profoundly impairs energy metabolism in primary human muscle cells.Endocrine connections · 2020Article
- VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.EMBO reports · 2020Article
- Is having a sweetheart enough to survive?Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2020Article
- Simvastatin re-sensitizes hepatocellular carcinoma cells to sorafenib by inhibiting HIF-1α/PPAR-γ/PKM2-mediated glycolysis.Journal of experimental & clinical cancer research : CR · 2020Article
- Association of statin therapy with incidence of type 2 diabetes among US Veterans.Journal of clinical cardiology and cardiovascular therapy · 2019Article
- Simvastatin Evokes An Unpredicted Antagonism For Tamoxifen In MCF-7 Breast Cancer Cells.Cancer management and research · 2019Article
- Evaluation of tamoxifen and simvastatin as the combination therapy for the treatment of hormonal dependent breast cancer cells.Toxicology reports · 2019Article
- Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea.Cardiovascular diabetology · 2018Observational
- Lipid-Protein Interactions Are Unique Fingerprints for Membrane Proteins.ACS central science · 2018Article
- Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue.International journal of endocrinology · 2018Review
- Solute Carriers in the Blood-Brain Barier: Safety in Abundance.Neurochemical research · 2017Review
- Mammalian Glucose Transporter Activity Is Dependent upon Anionic and Conical Phospholipids.The Journal of biological chemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveConsidering the increasing number of clinical observations indicating hyperglycemic effects of statins, this study was designed to measure the influence of statins on the uptake of glucose analogs by human cells derived from liver, adipose tissue, and skeletal muscle.
designFlow cytometry and scintillation counting were used to measure the uptake of fluorescently labeled or tritiated glucose analogs by differentiated visceral preadipocytes, skeletal muscle cells, skeletal muscle myoblasts, and contact-inhibited human hepatocellular carcinoma cells. A bioinformatics approach was used to predict the structure of human glucose transporter 1 (GLUT1) and to identify the presence of putative cholesterol-binding (cholesterol recognition/interaction amino acid consensus (CRAC)) motifs within this transporter. Mutagenesis of CRAC motifs in SLC2A1 gene and limited proteolysis of membrane GLUT1 were used to determine the molecular effects of statins.
resultsStatins significantly inhibit the uptake of glucose analogs in all cell types. Similar effects are induced by methyl-β-cyclodextrin, which removes membrane cholesterol. Statin effects can be rescued by addition of mevalonic acid, or supplementation with exogenous cholesterol. Limited proteolysis of GLUT1 and mutagenesis of CRAC motifs revealed that statins induce conformational changes in GLUTs.
conclusionsStatins impair glucose uptake by cells involved in regulation of glucose homeostasis by inducing cholesterol-dependent conformational changes in GLUTs. This molecular mechanism might explain hyperglycemic effects of statins observed in clinical trials.
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