The effect of hyperglycaemia on glucose disposal and insulin signal transduction in skeletal muscle

Skeletal muscle is an important tissue for the proper maintenance of glucose homeostasis as it accounts for the major portion of glucose disposal following infusion or ingestion of glucose. Thus, cellular mechanisms regulating glucose uptake in skeletal muscle have a major impact on whole-body glucose homeostasis. Glucose transport into skeletal muscle is a rate-limiting step for glucose utilization under physiological conditions and a site of insulin resistance in patients with non-insulin-dependent diabetes mellitus (NIDDM). Defects in insulin signalling have been coupled to impaired glucose uptake in skeletal muscle from NIDDM patients. Although the exact aetiology is unclear, genetic and environmental (high-energy diets combined with a sedentary lifestyle) factors contribute to the onset of NIDDM. Furthermore, hyperglycaemia is linked with insulin resistance. This chapter will consider mechanisms for glucose disposal in skeletal muscle, potential sites of insulin resistance in skeletal muscle in NIDDM patients and the impact of hyperglycaemia on insulin action.