Kroemer, Heyo Klaus

[["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","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"]]

[["dc.bibliographiccitation.artnumber","144"],["dc.bibliographiccitation.journal","Journal of Translational Medicine"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Grabe, Hans Joergen"],["dc.contributor.author","Assel, Heinrich"],["dc.contributor.author","Bahls, Thomas"],["dc.contributor.author","Doerr, Marcus"],["dc.contributor.author","Endlich, Karlhans"],["dc.contributor.author","Endlich, Nicole"],["dc.contributor.author","Erdmann, Pia"],["dc.contributor.author","Ewert, Ralf"],["dc.contributor.author","Felix, Stephan B."],["dc.contributor.author","Fiene, Beate"],["dc.contributor.author","Fischer, Tobias"],["dc.contributor.author","Flessa, Steffen"],["dc.contributor.author","Friedrich, Nele"],["dc.contributor.author","Gadebusch-Bondio, Mariacarla"],["dc.contributor.author","Salazar, Manuela Gesell"],["dc.contributor.author","Hammer, Elke"],["dc.contributor.author","Haring, Robin"],["dc.contributor.author","Havemann, Christoph"],["dc.contributor.author","Hecker, Michael"],["dc.contributor.author","Hoffmann, Wolfgang"],["dc.contributor.author","Holtfreter, Birte"],["dc.contributor.author","Kacprowski, Tim"],["dc.contributor.author","Klein, Kathleen"],["dc.contributor.author","Kocher, Thomas"],["dc.contributor.author","Kock, Holger"],["dc.contributor.author","Krafczyk, Janina"],["dc.contributor.author","Kuhn, Jana"],["dc.contributor.author","Langanke, Martin"],["dc.contributor.author","Lendeckel, Uwe"],["dc.contributor.author","Lerch, Markus M."],["dc.contributor.author","Lieb, Wolfgang"],["dc.contributor.author","Lorbeer, Roberto"],["dc.contributor.author","Mayerle, Julia"],["dc.contributor.author","Meissner, Konrad"],["dc.contributor.author","Schwabedissen, Henriette E. Meyer zu"],["dc.contributor.author","Nauck, Matthias"],["dc.contributor.author","Ott, Konrad"],["dc.contributor.author","Rathmann, Wolfgang"],["dc.contributor.author","Rettig, Rainer"],["dc.contributor.author","Richardt, Claudia"],["dc.contributor.author","Salje, Karen"],["dc.contributor.author","Schminke, Ulf"],["dc.contributor.author","Schulz, Andrea"],["dc.contributor.author","Schwab, Matthias"],["dc.contributor.author","Siegmund, Werner"],["dc.contributor.author","Stracke, Sylvia"],["dc.contributor.author","Suhre, Karsten"],["dc.contributor.author","Ueffing, Marius"],["dc.contributor.author","Ungerer, Saskia"],["dc.contributor.author","Voelker, Uwe"],["dc.contributor.author","Voelzke, Henry"],["dc.contributor.author","Wallaschofski, Henri"],["dc.contributor.author","Werner, Vivian"],["dc.contributor.author","Zygmunt, Marek T."],["dc.contributor.author","Kroemer, Heyo K."],["dc.date.accessioned","2018-11-07T09:39:59Z"],["dc.date.available","2018-11-07T09:39:59Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: Individualized Medicine aims at providing optimal treatment for an individual patient at a given time based on his specific genetic and molecular characteristics. This requires excellent clinical stratification of patients as well as the availability of genomic data and biomarkers as prerequisites for the development of novel diagnostic tools and therapeutic strategies. The University Medicine Greifswald, Germany, has launched the \"Greifswald Approach to Individualized Medicine\" (GANI_MED) project to address major challenges of Individualized Medicine. Herein, we describe the implementation of the scientific and clinical infrastructure that allows future translation of findings relevant to Individualized Medicine into clinical practice. Methods/design: Clinical patient cohorts (N > 5,000) with an emphasis on metabolic and cardiovascular diseases are being established following a standardized protocol for the assessment of medical history, laboratory biomarkers, and the collection of various biosamples for bio-banking purposes. A multi-omics based biomarker assessment including genome-wide genotyping, transcriptome, metabolome, and proteome analyses complements the multi-level approach of GANI_MED. Comparisons with the general background population as characterized by our Study of Health in Pomerania (SHIP) are performed. A central data management structure has been implemented to capture and integrate all relevant clinical data for research purposes. Ethical research projects on informed consent procedures, reporting of incidental findings, and economic evaluations were launched in parallel."],["dc.identifier.doi","10.1186/1479-5876-12-144"],["dc.identifier.isi","000338469800002"],["dc.identifier.pmid","24886498"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10153"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33415"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1479-5876"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Cohort profile: Greifswald approach to individualized medicine (GANI_MED)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","688"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","688"],["dc.bibliographiccitation.journal","BMC Research Notes"],["dc.bibliographiccitation.lastpage","6"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Meyer zu Schwabedissen, Henriette Elisabeth"],["dc.contributor.author","Siegmund, Werner"],["dc.contributor.author","Kroemer, Heyo Klaus"],["dc.contributor.author","Rollnik, Jens D."],["dc.date.accessioned","2019-04-30T12:38:18Z"],["dc.date.available","2019-04-30T12:38:18Z"],["dc.date.issued","2014"],["dc.description.abstract","BACKGROUND: Genetic factors as predictor of the individual outcome of drug therapy is one aim of personalized medicine approaches. CASE PRESENTATION: We report a drug metabolism based analysis of genetic polymorphisms in a Caucasian patient receiving fluvastatin and telmisartan experiencing myotoxicity (myalgia and moderate creatine kinase elevation). CONCLUSIONS: The obtained findings suggest that heterocygocity of cytochrome P450 CYP2C9 3 variant in combination with multidrug resistance-associated protein MRP2-24C > T functions as risk factor predisposing to experience drug-drug interaction combing those drugs."],["dc.identifier.doi","10.1186/1756-0500-7-688"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10966"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57892"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1756-0500"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Creatine kinase elevation caused by a combination of fluvastatin and telmisartan in a patient heterozygous for the CYP2C9 3 and ABCC2 -24C T variants: a case report"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]