Insulin action on skeletal muscle protein metabolism during catabolic states

Insulin plays a major role in the regulation of skeletal muscle protein tur nover but its mechanism of action is not fully understood, especially in vi vo during catabolic states. These aspects are presently reviewed. Insulin i nhibits the ATP-ubiquitin proteasome proteolytic pathway which is presumabl y the predominant pathway involved in the breakdown of muscle protein. Evid ence of the ability of insulin to stimulate muscle protein synthesis in viv o was also presented. Many catabolic states in rats, e.g. streptozotocin di abetes, glucocorticoid excess or sepsis-induced cytokines, resulted in a de crease in insulin action on protein synthesis or degradation. The effect of catabolic factors would therefore be facilitated. In contrast, the antipro teolytic action of insulin was improved during hyperthyroidism in man and e arly lactation in goats. Excessive muscle protein breakdown should therefor e be prevented. In other words, the anabolic hormone insulin partly control led the 'catabolic drive'. Advances in the understanding of insulin signall ing pathways and targets should provide information on the interactions bet ween insulin action, muscle protein turnover and catabolic factors. (C) Inr a/Elsevier, Paris.