Variable effect of CTLA4.Ig (abatacept) treatment on insulin receptor substrate (IRS)-1 and AKT phosphorylation in patients with rheumatoid arthritis (RA). (A) Improvement in disease activity in RA patients (n = 7) following treatment with abatacept for 12 weeks, from median disease activity score in 28 joints (DAS28) 5.9 to 4.8 (P = 0.046, Wilcoxon signed ranks test). (B) Treatment with abatacept had variable effects on the Homeostasis Model Assessment for insulin resistance (HOMA-IR) in RA patients with low or high baseline insulin resistance. (C) Protein extracts from periperhal blood mononuclear cells of the RA patients were analyzed by western blotting for the Ser312 and Ser473- phosphorylated forms of insulin resistance substrate (IRS)-1 and AKT, respectively, at baseline and after 12 weeks treatment with abatacept. (D) Quantitative analysis of p-Ser321 IRS-1 normalized to β-actin expression showed no significant change following treatment with abatacept. (E) Variable trend in p-AKT levels from baseline to week 12 of treatment with abatacept in RA patients with low or high baseline insulin resistance.