ABSTRACT
Insulin resistance is the linchpin for development of the cardiometabolic syndrome and type 2 diabetes. Resistance to the actions of insulin in skeletal muscle is important in development of systemic insulin resistance given that skeletal muscle normally accounts for approximately 75% of all insulin-mediated glucose disposal. However, the molecular mechanisms responsible for skeletal muscle insulin resistance remain poorly defi ned. Understanding the mechanisms by which skeletal muscle tissue develops resistance to insulin could provide attractive targets for therapeutic interventions. Th ere is emerging evidence of an integral relationship between chronic infl ammation, oxidative stress, and skeletal muscle insulin resistance due to circulating infl ammatory cytokines derived from adipose tissue (e.g., adipokines) or from local autocrine/paracrine eff ects of skeletal muscle-derived cytokines (e.g., myokines). Th is chapter is focused on the eff ects of infl ammatory cytokines and oxidative stress on insulin signaling in skeletal muscle and consequent development of systemic insulin resistance.
