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1.  Statins impair glucose uptake in human cells 
Considering 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.
Flow 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.
Statins 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.
Statins 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.
PMCID: PMC4212557  PMID: 25452863
Glucose Uptake; GLUT1; Pharmacological Therapy
2.  Transport of deoxy-d-glucose into lymphocytes of patients with polycystic ovary syndrome 
Endocrine  2014;47(2):618-624.
Polycystic ovary syndrome (PCOS) is linked to increased risk of insulin resistance and diabetes mellitus in patients’ later life. The aim of this study was to investigate uptake of deoxy-d-glucose by peripheral blood lymphocytes of PCOS patients with normal fasting plasma glucose and normal glucose tolerance test. The study involved 20 patients with PCOS with normal fasting plasma glucose and normal glucose in 60 and 120 min of oral glucose tolerance test, aged 18–32 (mean 23), BMI between 20 and 30 (mean 26). A control group consisted of 20 healthy women matched for glucose level (normoglycemia), aged 18–28 years (mean 23), BMI 20–25 (mean 23). Blood for the studies was collected in fasting conditions onto heparin. Lymphocytes were isolated within 2 h from collection by centrifuging. The intracellular transport into lymphocytes was studied using tritium-labeled deoxy-d-glucose and measured with a liquid scintillation counter. Radioactivity in curie per minute (cpm) was evaluated after 24 h. An initial examination was performed to check the presence of GLUT4 in peripheral blood lymphocytes of PCOS women. In all of the studied time points, the value of cpm for lymphocytes of PCOS patients was statistically significantly lower in comparison with the value obtained for lymphocytes of healthy women. However, the profile of deoxy-d-glucose uptake (d cpm) was the same for lymphocytes in both studied groups without statistically significant differences. In lymphocytes of PCOS patients, GLUT4 was detected. The obtained results indicate that PCOS affects the intracellular transport of deoxy-d-glucose into lymphocytes of PCOS patients with normal glucose level.
PMCID: PMC4204006  PMID: 24515540
Glucose transport; GLUT4; Lymphocytes; Insulin resistance; Diabetes
3.  Statins Impair Glucose Uptake in Tumor Cells1 
Neoplasia (New York, N.Y.)  2012;14(4):311-323.
Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at either transcriptional or protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered 18F-fluorodeoxyglucose (18F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting 18F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.
PMCID: PMC3349257  PMID: 22577346

Results 1-3 (3)