title: Effect of vildagliptin and pravastatin combination on cholesterol efflux in adipocytes.
abstract: Many reports suggested that some statins are almost ineffective in reducing triglycerides or enhancing HDL-C plasma levels, although statin treatment was still efficacious in reducing LDL-C. In diabetic dyslipidemic patients, it may therefore be necessary to use a combination therapy with other drugs to achieve either LDL-C- and triglyceride-lowering or HDL-C-enhancing goals. Such ineffectiveness of statins can be attributed to their effect on the liver X receptor (LXR) which regulates the expression of the ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. A decrease in the expression of these transporters eventually leads to decreased cholesterol efflux from peripheral tissues leading to low levels of HDL-C. Although manipulating the LXR pathway may complement the effects of statins, LXR synthetic ligands as T091317 have shown significant hypertriglyceridemic action which limits their use. We recently found that the antidiabetic drug vildagliptin stimulates LXR expression leading to increased ABCB1/ABCG1 expression which improves cholesterol efflux from adipocytes. Therefore, a combination of vildagliptin and statin may provide a solution without the hypertriglyceridemic action observed with LXR agonist. We hypothesize that a combination of vildagliptin and pravastatin will improve cholesterol efflux in adipocytes. Statin-treated 3T3-L1 adipocytes were treated with vildagliptin, and the expression of LXR-ABCA1/ABCG1 cascade and the cholesterol efflux were then determined. Our data indicate that a combination of vildagliptin and pravastatin significantly induces the expression of LXR-ABCA1/ABCG1 cascade and improves cholesterol efflux (P > 0.05) in adipocytes. Our data may explain, at least in part, the improvement in HDL-C levels observed in patients receiving both medications. © 2016 IUBMB Life, 68(7):535-543, 2016.
authors.affiliation: Maternal-Fetal Pharmacology and Bio-Development Laboratories, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Mostafa
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Hamdy
authors.affiliation: Maternal-Fetal Pharmacology and Bio-Development Laboratories, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Sherif Z
authors.initials: SZ
authors.lastname: Abdel-Rahman
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
authors.forename: Hala O
authors.initials: HO
authors.lastname: El-Mesallamy
mesh_terms: D041721:3T3-L1 Cells; D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics*; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000235:genetics*; D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives; D017667:Adipocytes / Q000187:drug effects / Q000473:pathology; D000818:Animals; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D008076:Cholesterol, HDL / Q000235:genetics; D050171:Dyslipidemias / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D050356:Lipid Metabolism / Q000235:genetics; D000071518:Liver X Receptors / Q000235:genetics*; D051379:Mice; D009570:Nitriles / Q000008:administration & dosage; D017035:Pravastatin / Q000008:administration & dosage; D011759:Pyrrolidines / Q000008:administration & dosage; D000077597:Vildagliptin
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D000218:Adamantane; D002784:Cholesterol; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000071518:Liver X Receptors; D009570:Nitriles; D017035:Pravastatin; D011759:Pyrrolidines; D000077597:Vildagliptin; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse
keywords: ABC transporters; adipocytes; cholesterol; pravastatin; vildagliptin