title: Insulin resistance: an adaptive mechanism becomes maladaptive in the current environment - an evolutionary perspective.
abstract: Human survival has relied upon the ability to withstand starvation through energy storage, the capacity to fight off infection by a proinflammatory immune response, and the ability to cope with physical stressors by an adaptive stress response. Energy storage, mainly as glycogen in liver and triglycerides in adipose tissue, is regulated by the anabolic actions of insulin. On the other hand, mobilization of stored energy during infection, trauma or stress is served by the temporary inhibition of insulin action (insulin resistance) in target tissues by proinflammatory cytokines and stress hormones. In the current environment, high energy intake, low physical activity, and chronic stress favor the storage of surplus fat in adipose tissue depots that far exceeds their storage capacity and liporegulation. Lipid overload in central fat depots initiates an inflammatory response and adipocyte dysfunction with resultant low-grade systemic inflammation and lipid overflow to peripheral tissues. In turn, proinflammatory cytokines and non-oxidized lipid metabolites, accumulated in liver and muscle cells, activate the mechanism of insulin resistance as would occur in the case of infection or stress. The same factors together with the ensuing insulin resistance further contribute to pancreatic β-cell dysfunction and ultimately to type 2 diabetes and cardiovascular disease. The present review supports the hypothesis that insulin resistance evolved as a physiological adaptive mechanism in human survival and that the same mechanism is inappropriately activated on a chronic basis in the current environment, leading to the manifestations of the metabolic syndrome.
authors.affiliation: Department of Endocrinology, Medical School, University of Ioannina, 45110 Ioannina, Greece. atsatsou@uoi.gr
authors.forename: Agathocles
authors.initials: A
authors.lastname: Tsatsoulis
authors.forename: Michalis D
authors.initials: MD
authors.lastname: Mantzaris
authors.forename: Sofia
authors.initials: S
authors.lastname: Bellou
authors.forename: Maria
authors.initials: M
authors.lastname: Andrikoula
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism / Q000502:physiology; D000818:Animals; D005075:Biological Evolution; D004777:Environment; D059647:Gene-Environment Interaction; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008954:Models, Biological; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology