title: Modulatory effect of insulin on T cell receptor mediated calcium signaling is blunted in long lasting type 1 diabetes mellitus.
abstract: Insulin significantly influences Ca(2+) signals evoked by various stimulants. In type 1 recent onset diabetes mellitus the proliferative response of T cells is significantly decreased. The number of clinical trials exploring the role of anti-CD3 monoclonal antibodies (mAb) as a therapeutic agent in recent onset diabetes mellitus type 1 is increasing last years. Therefore, a better understanding of the interplay between T cell receptor (TCR) dependent Ca(2+) increase, and insulin is of vital clinical significance. The aim of the study was to assess the effect of insulin on TCR evoked Ca(2+) responses in T lymphocytes obtained from healthy volunteers and patients suffering from long lasting diabetes mellitus type 1. Analysis was performed with use of the flow cytometer. We demonstrated that T cells ability to mobilize Ca(2+) was significantly reduced in long lasting diabetes mellitus type 1. Ca(2+) decrease achieved by the long term incubation with anti-CD3 mAb in T cells from healthy volunteers was restored by insulin. Strong interrelationship between baseline Ca(2+) level and plateau phase response to TCR stimulation was observed in the cytoplasm of cells pre-incubated with insulin from both healthy subjects and diabetic patients (r = 0.95, p < 0.0001 and r = 0.94, p < 0.0001, respectively). We postulate the existence of the interplay between TCR mediated activation and insulin. The TCR-insulin interplay is blunted in long lasting diabetes mellitus type 1. These observations may have an important implication for future therapeutic options in diabetes.
authors.affiliation: Department of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Marszałkowska 24, PL 00-576 Warszawa, Poland. demkow@litewska.edu.pl
authors.forename: Urszula
authors.initials: U
authors.lastname: Demkow
authors.forename: Paweł
authors.initials: P
authors.lastname: Winklewski
authors.forename: Olga
authors.initials: O
authors.lastname: Ciepiela
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Popko
authors.forename: Anna
authors.initials: A
authors.lastname: Lipińska
authors.forename: Anna
authors.initials: A
authors.lastname: Kucharska
authors.forename: Beata
authors.initials: B
authors.lastname: Michalska
authors.forename: Maria
authors.initials: M
authors.lastname: Wąsik
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D007328:Insulin; D011948:Receptors, Antigen, T-Cell; D002118:Calcium