Modulatory effect of insulin on T cell receptor mediated calcium signaling is blunted in long lasting type 1 diabetes mellitus

Insulin significantly influences ca2+ 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 ca2+ increase,and insulin is of vital clinical significance. the aim of the study was to assess the effect of insulin on tcr evoked ca2+ 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 ca2+ was significantly reduced in long lasting diabetes mellitus type 1. ca2+ 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 ca2+ 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. copyright © 2012 by institute of pharmacology polish academy of sciences.