{"doi":"10.1161/01.hyp.35.5.1092","title":"Aldose Reductase Inhibitor Improves Insulin-Mediated Glucose Uptake and Prevents Migration of Human Coronary Artery Smooth Muscle Cells Induced by High Glucose","abstract":"<jats:p>\n            <jats:italic>Abstract</jats:italic>\n            —We examined involvement  of the polyol pathway in high glucose–induced human coronary  artery smooth muscle cell (SMC) migration using Boyden’s chamber  method. Chronic glucose treatment for 72 hours potentiated, in a  concentration-dependent manner (5.6 to 22.2 mol/L),  platelet-derived growth factor (PDGF) BB–mediated SMC migration.  This potentiation was accompanied by an increase in PDGF BB binding,  because of an increased number of PDGF-β receptors, and this  potentiation was blocked by the aldose reductase inhibitor  epalrestat. Epalrestat at concentrations of 10 and 100 nmol/L inhibited  high glucose–potentiated (22.2 mmol/L), PDGF BB–mediated  migration. Epalrestat at 100 nmol/L inhibited a high glucose–induced  increase in the reduced/oxidized nicotinamide adenine  dinucleotide ratio and membrane-bound protein kinase C  (PKC) activity in SMCs. PKC inhibitors calphostin C (100  nmol/L) and chelerythrine (1 μmol/L) each inhibited high  glucose–induced, PDGF BB–mediated SMC migration. High  glucose–induced suppression of insulin-mediated  [\n            <jats:sup>3</jats:sup>\n            H]-deoxyglucose uptake, which was blocked by both  calphostin C (100 nmol/L) and chelerythrine (1 μmol/L), was  decreased by epalrestat (100 nmol/L). Chronic high glucose treatment  for 72 hours increased intracellular oxidative stress, which was  directly measured by flow cytometry using  carboxydichlorofluorescein diacetate bis-acetoxymethyl  ester, and this increase was significantly suppressed by epalrestat  (100 nmol/L). Antisense oligonucleotide to PKC-β  isoform inhibited high glucose–mediated changes in SMC migration,  insulin-mediated [\n            <jats:sup>3</jats:sup>\n            H]-deoxyglucose uptake, and oxidative  stress. These findings suggest that high glucose concentrations  potentiate SMC migration in coronary artery and that the aldose  reductase inhibitor epalrestat inhibits high  glucose–potentiated, PDGF BB–induced SMC migration, possibly through  suppression of PKC (PKC-β), impaired insulin-mediated glucose uptake,  and oxidative stress.\n          </jats:p>","journal":"Hypertension","year":2000,"id":676682,"datarank":1.6913735250469406,"base_score":3.332204510175204,"endowment":3.332204510175204,"self_citation_contribution":0.49983067652628066,"citation_network_contribution":1.1915428485206598,"self_endowment_contribution":0.49983067652628066,"citer_contribution":1.1915428485206598,"corpus_percentile":null,"corpus_rank":null,"citation_count":27,"citer_count":26,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":182579,"name":"Masakazu Kohno","orcid":null,"position":1,"is_corresponding":false},{"id":1768031,"name":"Hiroaki Kano","orcid":null,"position":2,"is_corresponding":false},{"id":1768032,"name":"Mieko Minami","orcid":null,"position":3,"is_corresponding":false},{"id":1477274,"name":"Junichi Yoshikawa","orcid":"0000-0003-1490-1558","position":4,"is_corresponding":false},{"id":1768029,"name":"Kenichi Yasunari","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Aldose Reductase Inhibitor Improves Insulin-Mediated Glucose Uptake and Prevents Migration of Human Coronary Artery Smooth Muscle Cells Induced by High Glucose","abstract":"<jats:p>\n            <jats:italic>Abstract</jats:italic>\n            —We examined involvement  of the polyol pathway in high glucose–induced human coronary  artery smooth muscle cell (SMC) migration using Boyden’s chamber  method. Chronic glucose treatment for 72 hours potentiated, in a  concentration-dependent manner (5.6 to 22.2 mol/L),  platelet-derived growth factor (PDGF) BB–mediated SMC migration.  This potentiation was accompanied by an increase in PDGF BB binding,  because of an increased number of PDGF-β receptors, and this  potentiation was blocked by the aldose reductase inhibitor  epalrestat. Epalrestat at concentrations of 10 and 100 nmol/L inhibited  high glucose–potentiated (22.2 mmol/L), PDGF BB–mediated  migration. Epalrestat at 100 nmol/L inhibited a high glucose–induced  increase in the reduced/oxidized nicotinamide adenine  dinucleotide ratio and membrane-bound protein kinase C  (PKC) activity in SMCs. PKC inhibitors calphostin C (100  nmol/L) and chelerythrine (1 μmol/L) each inhibited high  glucose–induced, PDGF BB–mediated SMC migration. High  glucose–induced suppression of insulin-mediated  [\n            <jats:sup>3</jats:sup>\n            H]-deoxyglucose uptake, which was blocked by both  calphostin C (100 nmol/L) and chelerythrine (1 μmol/L), was  decreased by epalrestat (100 nmol/L). Chronic high glucose treatment  for 72 hours increased intracellular oxidative stress, which was  directly measured by flow cytometry using  carboxydichlorofluorescein diacetate bis-acetoxymethyl  ester, and this increase was significantly suppressed by epalrestat  (100 nmol/L). Antisense oligonucleotide to PKC-β  isoform inhibited high glucose–mediated changes in SMC migration,  insulin-mediated [\n            <jats:sup>3</jats:sup>\n            H]-deoxyglucose uptake, and oxidative  stress. These findings suggest that high glucose concentrations  potentiate SMC migration in coronary artery and that the aldose  reductase inhibitor epalrestat inhibits high  glucose–potentiated, PDGF BB–induced SMC migration, possibly through  suppression of PKC (PKC-β), impaired insulin-mediated glucose uptake,  and oxidative stress.\n          </jats:p>","is_dataset_classified":null,"base_score":3.332204510175204,"endowment":3.332204510175204,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10818070","pmcid":null,"openalex_id":"https://openalex.org/W2144280697","authors":[],"funders":[],"total_grants":0,"fwci":0.8319,"citation_percentile":0.72626982,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2014,"count":2},{"year":2015,"count":1},{"year":2016,"count":6},{"year":2017,"count":1},{"year":2019,"count":1},{"year":2023,"count":1},{"year":2024,"count":2},{"year":2025,"count":1}],"oa_status":"closed","license":null,"oa_locations":[{"url":"https://www.ahajournals.org/doi/full/10.1161/01.HYP.35.5.1092","host_type":"publisher"},{"url":"https://doi.org/10.1161/01.hyp.35.5.1092","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10818070","host_type":"repository"}],"fields_of_study":["Aldose Reductase and Taurine","Nitric Oxide and Endothelin Effects","Adenosine and Purinergic Signaling"],"mesh_terms":["Becaplermin","Aldehyde Reductase","Arteriosclerosis","Cell Movement","Cells, Cultured","Coronary Vessels","Dose-Response Relationship, Drug","Enzyme Inhibitors","Glucose","Humans","Hypoglycemic Agents","Insulin","Platelet-Derived Growth Factor","Rhodanine","Proto-Oncogene Proteins c-sis","Thiazolidines"],"keywords":["Chelerythrine","Calphostin C","Aldose reductase inhibitor","Calphostin","Internal medicine","Endocrinology","Protein kinase C","Glucose uptake","Mesangial cell","Polyol pathway","Insulin","Aldose reductase","Oxidative stress","Glucose transporter","Chemistry","Biology","Biochemistry","Kinase","Diabetes mellitus","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T02:58:00.257431Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}