Genetic Dissection of the Physiological Role of Skeletal Muscle in Metabolic Syndrome

Abstract

The primary deficiency underlying metabolic syndrome is insulin resistance, in which insulin-responsive peripheral tissues fail to maintain glucose homeostasis. Because skeletal muscle is the major site for insulin-induced glucose uptake, impairments in skeletal muscle’s insulin responsiveness play a major role in the development of insulin resistance and type 2 diabetes. For example, skeletal muscle of type 2 diabetes patients and their offspring exhibit reduced ratios of slow oxidative muscle. These observations suggest the possibility of applying muscle remodeling to recover insulin sensitivity in metabolic syndrome. Skeletal muscle is highly adaptive to external stimulations such as exercise; however, in practice it is often not practical or possible to enforce the necessary intensity to obtain measurable benefits to the metabolic syndrome patient population. Therefore, identifying molecular targets for inducing muscle remodeling would provide new approaches to treat metabolic syndrome. In this review, the physiological properties of skeletal muscle, genetic analysis of metabolic syndrome in human populations and model organisms, and genetically engineered mouse models will be discussed in regard to the prospect of applying skeletal muscle remodeling as possible therapy for metabolic syndrome.