{"doi":"10.3389/fcell.2022.861644","title":"Dysregulated Erythroid Mg2+ Efflux in Type 2 Diabetes","abstract":"Hyperglycemia is associated with decreased Mg 2+ content in red blood cells (RBC), but mechanisms remain unclear. We characterized the regulation of Mg 2+ efflux by glucose in ex vivo human RBC. We observed that hemoglobin A 1C (HbA 1C ) values correlated with Na + -dependent Mg 2+ efflux (Na + /Mg 2+ exchange) and inversely correlated with cellular Mg content. Treatment of cells with 50 mM D-glucose, but not with sorbitol, lowered total cellular Mg (2.2 ± 0.1 to 2.0 ± 0.1 mM, p < 0.01) and enhanced Na + /Mg 2+ exchange activity [0.60 ± 0.09 to 1.12 ± 0.09 mmol/10 13 cell × h (flux units, FU), p < 0.05]. In contrast, incubation with selective Src family kinase inhibitors PP2 or SU6656 reduced glucose-stimulated exchange activation ( p < 0.01). Na + /Mg 2+ exchange activity was also higher in RBC from individuals with type 2 diabetes (T2D, 1.19 ± 0.13 FU) than from non-diabetic individuals (0.58 ± 0.05 FU, p < 0.01). Increased Na + /Mg 2+ exchange activity in RBC from T2D subjects was associated with lower intracellular Mg content. Similarly increased exchange activity was evident in RBC from the diabetic db / db mouse model as compared to its non-diabetic control ( p < 0.03). Extracellular exposure of intact RBC from T2D subjects to recombinant peptidyl-N-glycosidase F (PNGase F) reduced Na + /Mg 2+ exchange activity from 0.98 ± 0.14 to 0.59 ± 0.13 FU ( p < 0.05) and increased baseline intracellular Mg content (1.8 ± 0.1 mM) to normal values (2.1 ± 0.1 mM, p < 0.05). These data suggest that the reduced RBC Mg content of T2D RBC reflects enhanced RBC Na + /Mg 2+ exchange subject to regulation by Src family kinases and by the N-glycosylation state of one or more membrane proteins. The data extend our understanding of dysregulated RBC Mg 2+ homeostasis in T2D.","journal":"Frontiers in Cell and Developmental Biology","year":2022,"id":284863,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9596,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":802622,"name":"Alicia Rivera","orcid":"0000-0002-0433-6367","position":1,"is_corresponding":false},{"id":88930,"name":"Jay G. Wohlgemuth","orcid":null,"position":2,"is_corresponding":false},{"id":803051,"name":"Jeffrey S. Dlott","orcid":null,"position":3,"is_corresponding":false},{"id":803052,"name":"L. Michael Snyder","orcid":null,"position":4,"is_corresponding":false},{"id":54021,"name":"Seth L. Alper","orcid":"0000-0002-6228-2512","position":5,"is_corresponding":false},{"id":419660,"name":"José R. Romero","orcid":"0000-0001-8225-0772","position":6,"is_corresponding":false},{"id":963061,"name":"Ana Ferreira","orcid":"0000-0002-9171-6068","position":0,"is_corresponding":true}],"reference_count":95,"raw_metadata":null,"created_at":"2026-07-19T00:29:40.826853Z","pmid":"35445032","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":[]}