Inflammatory
arthritis is burdened by an increased risk of metabolic disorders.
Cytokines and other mediators in inflammatory diseases lead to
insulin resistance, diabetes and
hyperlipidemia. Accumulating evidence in the field of immunometabolism suggests that the cause-effect relationship between
arthritis and metabolic abnormalities might be bidirectional. Indeed, the immune response can be modulated by various factors such as environmental agents, bacterial products and
hormones.
Insulin is produced by pancreatic cells and regulates
glucose, fat metabolism and cell growth. The action of
insulin is mediated through the
insulin receptor (IR), localized on the cellular membrane of hepatocytes, myocytes and adipocytes but also on the surface of T cells, macrophages, and dendritic cells. In murine models, the absence of IR in T-cells coincided with reduced
cytokine production, proliferation, and migration. In macrophages, defective
insulin signaling resulted in enhanced glycolysis affecting the responses to pathogens. In this review, we focalize on the bidirectional cause-effect relationship between impaired
insulin signaling and
arthritis analyzing how
insulin signaling may be involved in the aberrant immune response implicated in
arthritis and how inflammatory mediators affect
insulin signaling. Finally, the effect of
glucose-lowering agents on
arthritis was summarized.