{"doi":"10.2337/db09-0868","title":"<i>N</i>-Glycosylation of Carnosinase Influences Protein Secretion and Enzyme Activity","abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE</jats:title>\n                  <jats:p>The (CTG)n polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion. Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1 secretion is changed under hyperglycemic conditions.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS</jats:title>\n                  <jats:p>N-glycosylation of CN-1 was either inhibited by tunicamycin in pCSII-CN-1–transfected Cos-7 cells or by stepwise deletion of its three putative N-glycosylation sites. CN-1 protein expression, N-glycosylation, and enzyme activity were assessed in cell extracts and supernatants. The influence of hyperglycemia on CN-1 enzyme activity in human serum was tested in homozygous (CTG)5 diabetic patients and healthy control subjects.</jats:p>\n                  <jats:p>Tunicamycin completely inhibited CN-1 secretion. Deletion of all N-glycosylation sites was required to reduce CN-1 secretion efficiency. Enzyme activity was already diminished when two sites were deleted. In pCSII-CN-1–transfected Cos-7 cells cultured in medium containing 25 mmol/l d-glucose, the immature 61 kilodaltons (kDa) CN-1 immune reactive band was not detected. This was paralleled by an increased GlcNAc expression in cell lysates and CN-1 expression in the supernatants. Homozygous (CTG)5 diabetic patients had significantly higher serum CN-1 activity compared with genotype-matched, healthy control subjects.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS</jats:title>\n                  <jats:p>We conclude that apart from the (CTG)n polymorphism in the signal peptide of CN-1, N-glycosylation is essential for appropriate secretion and enzyme activity. Since hyperglycemia enhances CN-1 secretion and enzyme activity, our data suggest that poor blood glucose control in diabetic patients might result in an increased CN-1 secretion even in the presence of the (CTG)5 allele.</jats:p>\n               </jats:sec>","journal":"Diabetes","year":2010,"id":595397,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1524616,"name":"Hannes Koeppel","orcid":null,"position":1,"is_corresponding":false},{"id":1524618,"name":"Frederick Pfister","orcid":null,"position":2,"is_corresponding":false},{"id":1524620,"name":"Verena Peters","orcid":null,"position":3,"is_corresponding":false},{"id":1524623,"name":"Sibylle Sauerhoefer","orcid":null,"position":4,"is_corresponding":false},{"id":1524624,"name":"Paula Sternik","orcid":null,"position":5,"is_corresponding":false},{"id":1524626,"name":"Paul Brinkkoetter","orcid":null,"position":6,"is_corresponding":false},{"id":606528,"name":"Hanswalter Zentgraf","orcid":null,"position":7,"is_corresponding":false},{"id":303933,"name":"Gerjan Navis","orcid":"0000-0002-0616-0166","position":8,"is_corresponding":false},{"id":504227,"name":"Robert H. Henning","orcid":"0000-0002-5135-4621","position":9,"is_corresponding":false},{"id":1524629,"name":"Jacob Van Den Born","orcid":null,"position":10,"is_corresponding":false},{"id":620015,"name":"Stephan J.L. Bakker","orcid":null,"position":11,"is_corresponding":false},{"id":1524632,"name":"Bart Janssen","orcid":null,"position":12,"is_corresponding":false},{"id":1524635,"name":"Fokko J. van der Woude","orcid":null,"position":13,"is_corresponding":false},{"id":1524638,"name":"Benito A. Yard","orcid":null,"position":14,"is_corresponding":false},{"id":1524614,"name":"Eva Riedl","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>N</i>-Glycosylation of Carnosinase Influences Protein Secretion and Enzyme Activity","abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE</jats:title>\n                  <jats:p>The (CTG)n polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion. Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1 secretion is changed under hyperglycemic conditions.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS</jats:title>\n                  <jats:p>N-glycosylation of CN-1 was either inhibited by tunicamycin in pCSII-CN-1–transfected Cos-7 cells or by stepwise deletion of its three putative N-glycosylation sites. CN-1 protein expression, N-glycosylation, and enzyme activity were assessed in cell extracts and supernatants. The influence of hyperglycemia on CN-1 enzyme activity in human serum was tested in homozygous (CTG)5 diabetic patients and healthy control subjects.</jats:p>\n                  <jats:p>Tunicamycin completely inhibited CN-1 secretion. Deletion of all N-glycosylation sites was required to reduce CN-1 secretion efficiency. Enzyme activity was already diminished when two sites were deleted. In pCSII-CN-1–transfected Cos-7 cells cultured in medium containing 25 mmol/l d-glucose, the immature 61 kilodaltons (kDa) CN-1 immune reactive band was not detected. This was paralleled by an increased GlcNAc expression in cell lysates and CN-1 expression in the supernatants. Homozygous (CTG)5 diabetic patients had significantly higher serum CN-1 activity compared with genotype-matched, healthy control subjects.</jats:p>\n               </jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS</jats:title>\n                  <jats:p>We conclude that apart from the (CTG)n polymorphism in the signal peptide of CN-1, N-glycosylation is essential for appropriate secretion and enzyme activity. Since hyperglycemia enhances CN-1 secretion and enzyme activity, our data suggest that poor blood glucose control in diabetic patients might result in an increased CN-1 secretion even in the presence of the (CTG)5 allele.</jats:p>\n               </jats:sec>","is_dataset_classified":null,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20460427","pmcid":"PMC2911063","openalex_id":"https://openalex.org/W2135241248","authors":[],"funders":[],"total_grants":0,"fwci":2.0917,"citation_percentile":0.8642154,"influential_citations":0,"citation_trend":[{"year":2012,"count":5},{"year":2013,"count":3},{"year":2014,"count":4},{"year":2015,"count":4},{"year":2016,"count":5},{"year":2017,"count":2},{"year":2018,"count":4},{"year":2019,"count":2},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":2},{"year":2024,"count":4},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://creativecommons.org/licenses/by-nc-nd/3.0/","oa_locations":[{"url":"https://diabetesjournals.org/diabetes/article-pdf/59/8/1984/398565/zdb00810001984.pdf","host_type":"journal"},{"url":"https://diabetesjournals.org/diabetes/article-pdf/59/8/1984/398565/zdb00810001984.pdf","host_type":"publisher"},{"url":"https://journals.org/diabetes/diabetes/article-pdf/59/8/1984/398565/zdb00810001984.pdf","host_type":"publisher"},{"url":"https://doi.org/10.2337/db09-0868","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/20460427","host_type":"repository"},{"url":"https://research.rug.nl/en/publications/e49a2aeb-fa1c-447d-ae47-4b096bfbafb2","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2911063","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2911063","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2911063?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Biochemical effects in animals","Regulation of Appetite and Obesity","Healthcare and Venom Research"],"mesh_terms":["Adult","Aged","Animals","Chlorocebus aethiops","Diabetes Mellitus","Diabetic Nephropathies","Dipeptidases","Genotype","Glycosylation","Hexosamines","Humans","Hyperglycemia","Middle Aged","Polymorphism, Genetic","Reference Values","Transfection","Tunicamycin","Gene Expression Regulation, Enzymologic","Mutagenesis, Site-Directed","Age of Onset","COS Cells","Genetic Predisposition to Disease"],"keywords":["Tunicamycin","Glycosylation","Secretion","Enzyme","Endocrinology","Internal medicine","Biology","Enzyme assay","Molecular biology","Biochemistry","Gene","Medicine","Unfolded protein response"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-27T17:21:51.125430Z","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":[]}