Modulatory effect of insulin on T cell receptor mediated calcium signaling is blunted in long lasting type 1 diabetes mellitus.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 1
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 and Affiliations
Urszula Demkow, Paweł Winklewski, Olga Ciepiela, Katarzyna Popko, Anna Lipińska, Beata Michalska, Maria Wąsik
Keywords
Related Articles
- EP ID EP150843
- DOI -
- Views 70
- Downloads 0
Hydrogen sulfide (H(2)S) - the third gas of interest for pharmacologists.
Nitric oxide (NO) and carbon monoxide (CO) synthesized from L-arginine by NO synthase and from heme by heme oxygenase, respectively, are the well-known neurotransmitters and are also involved in the regulation of vascula...
Effect of carnosine treatment on oxidative stress in serum, apoB-containing lipoproteins fraction and erythrocytes of aged rats.
One of the mechanisms underlying the aging process is proposed to be oxidative damage by free radicals. Carnosine (β-alanyl-L-histidine) is a dipeptide with antioxidant properties. In this study, we investigated the effe...
Melatonin in experimental seizures and epilepsy.
Although melatonin is approved only for the treatment of jet-lag syndrome and some types of insomnia, clinical data suggest that it is effective in the adjunctive therapy of osteoporosis, cataract, sepsis, neurodegenerat...
Single centre 20 year survey of antiepileptic drug-induced hypersensitivity reactions.
Background: Epilepsy is a chronic neurological disease which affects about 1% of the human population. There are 50 million patients in the world suffering from this disease and 2 million new cases per year are observed....
Nicotine dependence - human and animal studies, current pharmacotherapies and future perspectives.
Nicotine dependence is a disease of constantly growing importance. This mini-review describes the effects of nicotine in humans and focuses on the various laboratory animal models developed to study the dependence-relate...