POTENTIAL ROLE OF REDOX SENSITIVE SERINE KINASE PATHWAYS IN THE PATHOGENESIS OF INSULIN RESISTANCE IN RHEUMATOID ARTHRITIS

Objectives: Insulin resistance and oxidative stress have been reported in rheumatoid arthritis (RA). However, the molecular basis of insulin resistance in RA is not clearly understood. Recent studies have documented the role of redox sensitive serine kinase pathways in insulin resistance. The aim of the study is to investigate insulin resistance, oxidative stress andlymphocyte redox sensitive - nuclear factor - kB (NF-kB), c-Jun N-terminal kinase (JNK) and p38 mitogen activated protein kinase (p38MAPK) pathways in RA subjects.Methods: Twenty newly diagnosed RA patients and 20 healthy volunteers in the age group of 30-50 years were included in this study. Overnight fasting blood was collected from the subjects, red blood cells, lymphocytes and plasma were separated using Ficoll hypaque. Blood oxidative stress parameters, fasting glucose and insulin were estimated. Redox sensitive serine kinase pathways in lymphocytes also studied. Results: The fasting insulin and HOMA-IR were significantly (p<0.001) higher in RA subjects compared to control subjects. Lymphocyte and erythrocyte reduced glutathione, erythrocyte catalase activity and plasma total antioxidant capacity were significantly (p<0.001) lower in RA subjects. Plasma MDA levels were significantly (p<0.001) higher in RA subjects. Western blotting analysis shows activation of NF-kB pathway in the lymphocytes of RA subjects. There was no significant change in the lymphocyte p38MAPK and JNK pathways between RA and control subjects. Conclusion: Further studies which explores the role of redox sensitive serine kinase pathways on insulin action in target tissues of insulin will help in the identification of novel therapeutic target for insulin resistance and its complications in RA.