Figure 4. Possible pathway mediating insulin resistance in subjects with post-streptococcal anti-PDI autoantibodies.

Streptococcal infections induce production of anti-Streptolysin O antibodies (ASLO), some of which share a common determinant with PDI. Molecular mimicry leads to inhibition of PDI which among other functions reduces and degrades insulin. The disulfide bonds of insulin are generated on the preproinsulin peptide, and thus reduction of any of the two disulfide bonds of insulin results in irreversible changes in activity. We hypothesize that lower degradation of insulin by PDI in the presence of anti-PDI antibodies result in higher insulin levels and insulin resistance.