Mechanisms and Linkage of Insulin Signaling, Resistance, and Inflammation

Abstract

Background: Chronic inflammation is responsible for low insulin sensitivity, making obesity a major risk factor for developing insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. Increased expression of inflammatory cytokines activates several signaling pathways, consequently leading to the accumulation of fats in adipocytes and contributing to the pathogenesis of insulin resistance. Aim: The review aimed to provide an overview of the potential molecular correlation between the insulin signaling pathway and the inflammatory process in addition to their linkage to the development of insulin resistance and other metabolic diseases, with an exploration of the possibility of using drugs that target inflammation in the management of diabetes. Results: Based on the obtained data from the latest literature, the source of cytokines in insulin-resistant states is the insulin targets themselves including the adipose tissue and liver, but to a greater extent the activated macrophages. Prolonged inflammation in these tissues may result in systemic insulin resistance via endocrine signaling and localized insulin resistance by paracrine/autocrine cytokine signaling. Conclusion: Inflammation is involved in the pathogenesis of insulin resistance and diabetes type 2, consequently, in the management of insulin resistance, antiinflammatory agents may benefit, and the risk assessment may benefit from the use of inflammatory biomarkers in such disorders.