[Phylogenesis, etiology and pathogenesis of insulin resistance. Differences from type II diabetes mellitus]

We believe that etiological factor of insulin resistance is phylogenetically late formation of insulin and its specific functionality, i.e., providing energy substrates for the biological function of locomotion. According to biological subordination, insulin cannot change regulation formed at the early stages of phylogenesis in all cells, including those that become insulin-dependent at the late stages of phylogenesis. This involves a) beta-oxidation of fatty acids in the mitochondria, b) synthesis of C 16:0 palmitic saturated fatty acid, c) glucose metabolism in pro- and eukaryotes, d) regulation of biochemical reactions in insulin-independent cells, e) humoral effects of mediators at the level of paracrine cell communities which are structural and functional units of all internal organs, and f) hormonal regulation at the entire organism level. Pathogenetic factors of insulin resistance are biochemical and functional disorders occurring in vivo upon activation of biological functions and reactions that formed phylogenetically earlier than insulin. During phylogenesis the insulin system has intrinsically built up over the regulatory mechanisms of mitochondria, early unicellular organisms and paracrine cell communities. Insulin functionally interacts with them all, but it cannot abolish the effects of any phylogenetically earlier humoral mediator. Insulin resistance is a pathophysiological disparity between humoral regulation of metabolism at the level of phylogenetically earlier paracrine cell communities and at the level of phylogenetically late total organism, on the one hand, and successive phylogenetic formation of passive cellular uptake of fatty acids as unesterified fatty acids and later triglycerides, on the other. If insulin resistance results from changes in the primary structure of transport proteins, in glucose storage and cellular insulin reception, it can be referred to as type II diabetes mellitus.