Regulation of tissue insulin sensitivity as a mechanism of functional priority: implications for adaptation, survival, and rehabilitation

Abstract

Background. Insulin Resistance (IR) is traditionally regarded as one of the key mechanisms underlying metabolic syndrome, type 2 diabetes mellitus, and associated cardiovascular complications. However, alterations in insulin sensitivity also occur during fasting, physical exercise, pregnancy, acute stress, trauma, and inflammation, suggesting their potential adaptive role in the regulation of energy metabolism. Aim. To summarize current evidence on the role of tissue insulin sensitivity in systemic immunometabolic adaptation and to substantiate the concept of its regulation as a mechanism of functional priority. Materials and Methods. A literature search for the narrative review was conducted in PubMed, Scopus, Web of Science, and Google Scholar. Data synthesis was performed using conceptual and integrative approaches. The study was carried out as a private initiative of the authors, without grant support and state registration of the topic. Research Ethics. Only sources that complied with current bioethical standards were selected for the analysis. Results. Available evidence indicates that alterations in insulin sensitivity are tissue-specific and may serve adaptive functions. During acute inflammation, activation of the cytokine network, the hypothalamic-pituitary-adrenal axis, the sympathoadrenal system, and other counter-regulatory mechanisms is accompanied by stress hyperglycemia, mobilization of energy substrates, and selective reduction of insulin sensitivity in skeletal muscle and adipose tissue. These changes increase the availability of energy resources for innate immune cells, the central nervous system, and other vital structures. Regulation of tissue insulin sensitivity is proposed as a mechanism of functional priority that ensures redistribution of resources according to the organism's adaptive needs. The concept of immunometabolic allostasis is substantiated, according to which insulin resistance may represent not only a manifestation of metabolic pathology but also a component of a coordinated adaptive response. Acute post-traumatic and low-grade sterile inflammation associated with metabolic syndrome appear to share common mechanisms of neuroendocrine regulation. Conclusions. Tissue insulin sensitivity may be regarded as an important component of systemic immunometabolic adaptation. The proposed concept of functional priority provides a basis for considering the regulation of insulin sensitivity as one of the mechanisms involved in the redistri-bution of energy resources among functional systems according to their importance for adaptation, survival, and recovery.