In diseases with concomitant oxidative stress, chronic multi-hormonal resistances could be detected. The most conspicuous component of these resistances is insulin resistance, but also leptin, erythropoietin, acetylcholine, triiodothyronine and glucagon-like peptide-1 resistances also occur. On the other hand, in oxidative stress, abnormal tyrosines, for instance, meta- and ortho-tyrosine are also produced and incorporated into the proteins through the translational process. In case these modified proteins are components of the intracellular signalling pathways, a hormonal resistance may develop. The above-mentioned hormones, owning overlapping signalling pathways at the insulin receptor substrate, develop an abnormal tyrosine phosphorylation dependent chronic multi-hormonal resistance. A few weeks free of oxidative stress or the use of antioxidant therapy are required to provide a return from this resistance, which return may be further supported by the supplementation of physiological para-tyrosine and by the add-on therapy of a pharmacological dose of glucagon-like peptide-1 receptor agonist, which is able to bypass the critical insulin receptor substrate signalling.
Keywords: chronic hormonal resistance; diabetes mellitus; glucagon-like protein-1 receptor agonist; insulin receptor substrate; meta-tyrosine; ortho-tyrosine; oxidative stress; tyrosine phosphorylation.