Kroemer, Heyo Klaus

[["dc.bibliographiccitation.firstpage","167"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell and Tissue Research"],["dc.bibliographiccitation.lastpage","176"],["dc.bibliographiccitation.volume","377"],["dc.contributor.author","Farenholtz, Jacob"],["dc.contributor.author","Artelt, Nadine"],["dc.contributor.author","Blumenthal, Antje"],["dc.contributor.author","Endlich, Karlhans"],["dc.contributor.author","Kroemer, Heyo K."],["dc.contributor.author","Endlich, Nicole"],["dc.contributor.author","von Bohlen und Halbach, Oliver"],["dc.date.accessioned","2020-12-10T14:10:38Z"],["dc.date.available","2020-12-10T14:10:38Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00441-019-03008-8"],["dc.identifier.eissn","1432-0878"],["dc.identifier.issn","0302-766X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70826"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Expression of Slc35f1 in the murine brain"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1069"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.lastpage","1077"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Rühle, Frank"],["dc.contributor.author","Weis, Tanja"],["dc.contributor.author","Homuth, Georg"],["dc.contributor.author","Keller, Andreas"],["dc.contributor.author","Franke, Jennifer"],["dc.contributor.author","Peil, Barbara"],["dc.contributor.author","Bermejo, Justo Lorenzo"],["dc.contributor.author","Frese, Karen"],["dc.contributor.author","Huge, Andreas"],["dc.contributor.author","Witten, Anika"],["dc.contributor.author","Vogel, Britta"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Völker, Uwe"],["dc.contributor.author","Ernst, Florian"],["dc.contributor.author","Teumer, Alexander"],["dc.contributor.author","Ehlermann, Philipp"],["dc.contributor.author","Zugck, Christian"],["dc.contributor.author","Friedrichs, Frauke"],["dc.contributor.author","Kroemer, Heyo"],["dc.contributor.author","Dörr, Marcus"],["dc.contributor.author","Hoffmann, Wolfgang"],["dc.contributor.author","Maisch, Bernhard"],["dc.contributor.author","Pankuweit, Sabine"],["dc.contributor.author","Ruppert, Volker"],["dc.contributor.author","Scheffold, Thomas"],["dc.contributor.author","Kühl, Uwe"],["dc.contributor.author","Schultheiss, Hans-Peter"],["dc.contributor.author","Kreutz, Reinhold"],["dc.contributor.author","Ertl, Georg"],["dc.contributor.author","Angermann, Christiane"],["dc.contributor.author","Charron, Philippe"],["dc.contributor.author","Villard, Eric"],["dc.contributor.author","Gary, Françoise"],["dc.contributor.author","Isnard, Richard"],["dc.contributor.author","Komajda, Michel"],["dc.contributor.author","Lutz, Matthias"],["dc.contributor.author","Meitinger, Thomas"],["dc.contributor.author","Sinner, Moritz F."],["dc.contributor.author","Wichmann, H.-Erich"],["dc.contributor.author","Krawczak, Michael"],["dc.contributor.author","Ivandic, Boris"],["dc.contributor.author","Weichenhan, Dieter"],["dc.contributor.author","Gelbrich, Goetz"],["dc.contributor.author","El-Mokhtari, Nour-Eddine"],["dc.contributor.author","Schreiber, Stefan"],["dc.contributor.author","Felix, Stephan B."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Pfeufer, Arne"],["dc.contributor.author","Hübner, Norbert"],["dc.contributor.author","Kääb, Stefan"],["dc.contributor.author","Arbustini, Eloisa"],["dc.contributor.author","Rottbauer, Wolfgang"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Stoll, Monika"],["dc.contributor.author","Katus, Hugo A."],["dc.date.accessioned","2017-09-07T11:46:19Z"],["dc.date.available","2017-09-07T11:46:19Z"],["dc.date.issued","2014"],["dc.description.abstract","Aims Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. Methods and reuslts Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 x 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. Conclusion The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM."],["dc.identifier.doi","10.1093/eurheartj/eht251"],["dc.identifier.gro","3142146"],["dc.identifier.isi","000335813500015"],["dc.identifier.pmid","23853074"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5044"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Bndesministerium fur Bildung und Forschung' (BMBF)"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1522-9645"],["dc.relation.issn","0195-668X"],["dc.title","A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","860"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Progress in Neuro-Psychopharmacology and Biological Psychiatry"],["dc.bibliographiccitation.lastpage","866"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Lucht, Michael J."],["dc.contributor.author","Barnow, Sven"],["dc.contributor.author","Sonnenfeld, Christine"],["dc.contributor.author","Rosenberger, Albert"],["dc.contributor.author","Grabe, Hans Joergen"],["dc.contributor.author","Schroeder, Winnie"],["dc.contributor.author","Voelzke, Henry"],["dc.contributor.author","Freyberger, Harald J."],["dc.contributor.author","Herrmann, Falko H."],["dc.contributor.author","Kroemer, Heyo K."],["dc.contributor.author","Rosskopf, Dieter"],["dc.date.accessioned","2018-11-07T08:27:32Z"],["dc.date.available","2018-11-07T08:27:32Z"],["dc.date.issued","2009"],["dc.description.abstract","Associations of oxytocin receptor gene (OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin OXTR rs53576 A/A genotype showed lower positive affect scores (F=5.532, df=1; p=0.019). This effect was restricted to males (F=13.098, df=1; p=0.00047). Haplotypes constructed with the three markers were associated with positive affect (p=0.0012), negative affect (p<0.0001) and emotional loneliness (p<0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (T=2.247, p=0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ. (C) 2009 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.pnpbp.2009.04.004"],["dc.identifier.isi","000268370100016"],["dc.identifier.pmid","19376182"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16226"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Pergamon-elsevier Science Ltd"],["dc.relation.issn","0278-5846"],["dc.title","Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","DMW - Deutsche Medizinische Wochenschrift"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Kroemer, H. K."],["dc.contributor.author","Hasenfuß, G."],["dc.contributor.author","Erdmann, E."],["dc.date.accessioned","2017-09-07T11:46:19Z"],["dc.date.available","2017-09-07T11:46:19Z"],["dc.date.issued","2014"],["dc.description.abstract","Die 80.  Jahrestagung der Deutschen Gesellschaft für Kardiologie, Herz- und Kreislaufforschung steht unter dem Thema „Kardiologie 2020 – von der Intervention zu Prävention und Regeneration“."],["dc.identifier.doi","10.1055/s-0034-1369978"],["dc.identifier.gro","3142149"],["dc.identifier.isi","000334180900004"],["dc.identifier.pmid","24722930"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/5077"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1439-4413"],["dc.relation.issn","0012-0472"],["dc.title","Cardiology: Innovative Medizin von molekularer Diagnostics bis modern interventional Technologie"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Pharmacogenetics and genomics"],["dc.bibliographiccitation.lastpage","18"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Meyer zu Schwabedissen, Henriette E."],["dc.contributor.author","Albers, Martin"],["dc.contributor.author","Baumeister, Sebastian E."],["dc.contributor.author","Rimmbach, Christian"],["dc.contributor.author","Nauck, Matthias"],["dc.contributor.author","Wallaschofski, Henri"],["dc.contributor.author","Siegmund, Werner"],["dc.contributor.author","Völzke, Henry"],["dc.contributor.author","Kroemer, Heyo K."],["dc.date.accessioned","2018-08-20T13:02:42Z"],["dc.date.available","2018-08-20T13:02:42Z"],["dc.date.issued","2015"],["dc.description.abstract","BACKGROUND: The efficacy of statins, which are used commonly in primary and secondary prevention of cardiovascular diseases, shows a wide range of interindividual variability. Genetic variants of OATP1B1, a hepatic uptake transporter, can modify access of statins to its therapeutic target, thereby potentially altering drug efficacy. We studied the impact of genetic variants of OATP1B1 on the lipid-lowering efficacy of statins in a population-based setting. MATERIALS AND METHODS: The basis of the analysis was the Study of Health in Pomerania, a cohort of 2732 men and women aged 20-81 years. Included in the statistical analysis to evaluate the impact of OATP1B1 on therapeutic efficacy of statins were 214 individuals diagnosed with dyslipidaemia during initial recruitment and receiving statins during the 5-year follow-up. RESULTS: Analysing the impact of the OATP1B1 genotype, we observed a trend for lower statin-induced total cholesterol reduction in carriers of the SLCO1B1 512C variant. Restricting the analysis to patients receiving simvastatin, pravastatin, lovastatin and fluvastatin indicated a statistically significant association of the OATP1B1 genotype on lipid parameters at the 5-year follow-up. No such effect was observed for atorvastatin. Calculation of achievement of treatment goals according to the NCEP-ATPIII guidelines showed a lower rate of successful treatment when harbouring the mutant allele for patients taking simvastatin (46.7 vs. 73.9%). A similar trend was observed for pravastatin (34.4 vs. 70.4%). CONCLUSION: Genetic variants of OATP1B1 leading to impaired hepatic uptake of statins translated into reduced drug efficacy in a population-based cohort."],["dc.identifier.doi","10.1097/FPC.0000000000000098"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15443"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1744-6872"],["dc.title","Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify the therapeutic efficacy of statins in a population-based cohort"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","108"],["dc.bibliographiccitation.journal","Biochemical Pharmacology"],["dc.bibliographiccitation.lastpage","119"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Monzel, Judith V."],["dc.contributor.author","Budde, Thomas"],["dc.contributor.author","Meyer Zu Schwabedissen, Henriette E."],["dc.contributor.author","Schwebe, Matthias"],["dc.contributor.author","Bien-Möller, Sandra"],["dc.contributor.author","Lutjohann, Dieter"],["dc.contributor.author","Kroemer, Heyo K."],["dc.contributor.author","Jedlitschky, Gabriele"],["dc.contributor.author","Grube, Markus"],["dc.date.accessioned","2018-08-17T13:13:19Z"],["dc.date.available","2018-08-17T13:13:19Z"],["dc.date.issued","2017"],["dc.description.abstract","The anthracycline-mediated cardiotoxicity is still not completely understood. To examine the impact of cholesterol metabolism and transport in this context, cholesterol and oxysterol levels as well as the expression of the cholesterol transporters ABCA1 and ABCG1 were analyzed in doxorubicin-treated HL-1 murine cardiomyocytes as well as in mouse model for acute doxorubicin-induced cardiotoxicity. Doxorubicin-treated HL-1 cells exhibited enhanced cholesterol (153+/-20% of control), oxysterol (24S-hydroxycholesterol: 206+/-29% of control) and cholesterol precursor levels (lathosterol: 122+/-12% of control; desmosterol: 188+/-10% of control) indicating enhanced cholesterol synthesis. Moreover, abca1 and abcg1 were upregulated on mRNA, protein and functional level caused by a doxorubicin-mediated activation of the nuclear receptor LXR. In addition, the oxysterols not only induced the abca1 and abcg1 in HL-1 cells but also enhanced the expression of endothelin-1 and transforming growth factor-beta, which have already been identified as important factors in doxorubicin-induced cardiotoxicity. These in vitro findings were verified in a murine model for acute doxorubicin-induced cardiotoxicity, demonstrating elevated cardiac (2.1+/-0.2vs. 3.6+/-1.0ng/mg) and systemic cholesterol levels (105.0+/-8.4vs. 130.0+/-4.3mg/dl), respectively, as well as enhanced oxysterol levels such as cardiac 24S-hydroxycholesterol (2.1+/-0.2vs. 3.6+/-1.0ng/mg). In line with these findings cardiac mRNA expression of abca1 (303% of control) and abcg1 (161% of control) was induced. Taken together, our data demonstrate enhanced cholesterol and oxysterol levels by doxorubicin, resulting in a LXR-dependent upregulation of abca1 and abcg1. In this context, the cytotoxic effects of oxysterols and their impact on cardiac gene expression should be considered as an important factor in doxorubicin-induced cardiotoxicity."],["dc.identifier.doi","10.1016/j.bcp.2017.08.008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15396"],["dc.language.iso","en"],["dc.notes.status","fcwi"],["dc.relation.eissn","0006-2952"],["dc.title","Doxorubicin enhances oxysterol levels resulting in a LXR-mediated upregulation of cardiac cholesterol transporters"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","665"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","DMW - Deutsche Medizinische Wochenschrift"],["dc.bibliographiccitation.lastpage","666"],["dc.bibliographiccitation.volume","138"],["dc.contributor.author","Lieb, Wolfgang"],["dc.contributor.author","Grabe, Hans Joergen"],["dc.contributor.author","Kroemer, Heyo K."],["dc.date.accessioned","2018-11-07T09:26:57Z"],["dc.date.available","2018-11-07T09:26:57Z"],["dc.date.issued","2013"],["dc.identifier.isi","000319185200017"],["dc.identifier.pmid","23512371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30422"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.relation.issn","0012-0472"],["dc.title","Research projects aimed at Enhancing personalized Medicine at the Clinic"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.subtype","letter_note"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","105"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Thrombosis and Haemostasis"],["dc.bibliographiccitation.lastpage","115"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Schaletzki, Yvonne"],["dc.contributor.author","Kromrey, Marie-Luise"],["dc.contributor.author","Broderdorf, Susanne"],["dc.contributor.author","Hammer, Elke"],["dc.contributor.author","Grube, Markus"],["dc.contributor.author","Hagen, Paul"],["dc.contributor.author","Sucic, Sonja"],["dc.contributor.author","Freissmuth, Michael"],["dc.contributor.author","Völker, Uwe"],["dc.contributor.author","Greinacher, Andreas"],["dc.contributor.author","Rauch, Bernhard H."],["dc.contributor.author","Kroemer, Heyo K."],["dc.contributor.author","Jedlitschky, Gabriele"],["dc.date.accessioned","2018-08-20T12:40:06Z"],["dc.date.available","2018-08-20T12:40:06Z"],["dc.date.issued","2017"],["dc.description.abstract","The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit beta3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter."],["dc.identifier.doi","10.1160/TH16-01-0045"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15439"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","0340-6245"],["dc.title","Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1562"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Drug Metabolism and Disposition"],["dc.bibliographiccitation.lastpage","1568"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Hubeny, Andrea"],["dc.contributor.author","Keiser, Markus"],["dc.contributor.author","Oswald, Stefan"],["dc.contributor.author","Jedlitschky, Gabriele"],["dc.contributor.author","Kroemer, Heyo K."],["dc.contributor.author","Siegmund, Werner"],["dc.contributor.author","Grube, Markus"],["dc.date.accessioned","2018-08-20T13:06:39Z"],["dc.date.available","2018-08-20T13:06:39Z"],["dc.date.issued","2016"],["dc.description.abstract","Important antimalarial drugs, including quinolines, act against blood schizonts by interfering with hemoglobin metabolism. To reach their site of action, these compounds have to cross the plasma membrane of red blood cells (RBCs). Organic cation transporters (OCTs) and organic anion transporting polypeptides (OATPs) are important uptake transporters and interesting candidates for local drug transport. We therefore studied their interaction with antimalarial compounds (quinine, chloroquine, mefloquine, pyrimethamine, artemisinin, and artesunate) and characterized the expression of OATP1A2 and OATP2B1 in RBCs. Competition assays using transporter-overexpressing Madin-Darby canine kidney (MDCKII) cells and the model substrate estrone-3-sulfate identified quinine and chloroquine as potent inhibitors of OATP1A2 function (IC50 quinine: 0.7 +/- 1.2 microM; chloroquine: 1.0 +/- 1.5 microM), but no or only moderate effects were observed for OATP2B1. Subsequently, quinine was identified as a substrate of OATP1A2 (Km 23.4 microM). The OATP1A2-mediated uptake was sensitive to the OATP1A2-specific inhibitor naringin. Both OATPs were expressed in human RBCs, and ex vivo transport studies demonstrated naringin-sensitive accumulation of quinine in these cells (60 pmol versus 38 pmol/5 x 10(5) RBCs). Additional transport studies using OCT1-3 and organic cation transporter novel type 1 (OCTN1) indicated only significant quinine uptake by OCT1, which was not detected in RBCs. In conclusion, our data demonstrate expression of OATP2B1 and OATP1A2 in RBCs as well as OATP1A2-mediated uptake of quinine. Therefore, modulation of OATP1A2 function may affect quinine uptake into erythrocytes."],["dc.identifier.doi","10.1124/dmd.116.069807"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15444"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","0090-9556"],["dc.title","Expression of Organic Anion Transporting Polypeptide 1A2 in Red Blood Cells and Its Potential Impact on Antimalarial Therapy"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","775"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Diabetes"],["dc.bibliographiccitation.lastpage","784"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Schwabedissen, Henriette E. Meyer zu"],["dc.contributor.author","Boettcher, Kerstin"],["dc.contributor.author","Steiner, Tobias"],["dc.contributor.author","Schwarz, Ute I."],["dc.contributor.author","Keiser, Markus"],["dc.contributor.author","Kroemer, Heyo K."],["dc.contributor.author","Siegmund, Werner"],["dc.date.accessioned","2018-11-07T09:44:27Z"],["dc.date.available","2018-11-07T09:44:27Z"],["dc.date.issued","2014"],["dc.description.abstract","Organic anion transporting polypeptide OATP1B3 is a membrane-bound drug transporter that facilitates cellular entry of a variety of substrates. Most of the previous studies focused on its hepatic expression and function in hepatic drug elimination. In this study, we report expression of OATP1B3 in human pancreatic tissue, with the abundance of the transporter localized in the islets of Langerhans. Transport studies using OATP1B3-overexpressing MDCKII cells revealed significant inhibition of the cellular uptake of the known substrate cholecystokinin-8 in the presence of the insulinotropic antidiabetes compounds tolbutamide, glibenclamide, glimepiride, and nateglinide and identified glibenclamide as a novel substrate of OATP1B3. Sulfonylurea derivatives exert their insulinotropic effect by binding to the SUR1 subunit of the K-ATP channels inducing insulin secretion in -cells. Here, we show that transient overexpression of human OATP1B3 in a murine -cell line (MIN6)which exhibits glucose and glibenclamide-sensitive insulin secretionsignificantly enhances the insulinotropic effect of glibenclamide without affecting glucose-stimulated insulin secretion. Taken together, our data provide evidence that the drug transporter OATP1B3 functions as a determinant of the insulinotropic effect of glibenclamide on the tissue level. Changes in transport activity based on drug-drug interactions or genetic variability may therefore influence glibenclamide efficacy."],["dc.identifier.doi","10.2337/db13-1005"],["dc.identifier.isi","000331110000042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34397"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Diabetes Assoc"],["dc.relation.issn","1939-327X"],["dc.relation.issn","0012-1797"],["dc.title","OATP1B3 Is Expressed in Pancreatic beta-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]