Metabolism in peripheral tissues in cancer patients

Cancer patients have increased insulin resistance in skeletal muscles and probably also in the liver. The insulin production in response to a glucose challenge is decreased. This is associated with decreased glucose uptake in peripheral tissues and increased gluconeogenesis from amino acids, lactate, and glycerol. The correlation between the insulin response to a glucose challenge and the activities of glycolytic and oxidative rate-limiting enzymes in muscle tissue suggests a common denominator for these metabolic alterations. The most prominent feature in alteration of lipid metabolism is a reduction of body fat, probably dependent on increased lipolysis. The released fatty acids are oxidized outside the tumor mass. Species characteristics may be important for the degree of hyperlipidemia. Wasting of the skeletal muscle mass is caused by decreased protein synthesis and probably increased degradation. Anorexia can induce but not entirely explain this altered protein metabolism. Decreased physical activity may be another important factor for the depressed protein synthesis. Total parenteral nutrition (TPN) improves the muscle protein synthesis. The mechanism behind increased fractional degradation of muscle proteins in vitro is not clear, but it may be coupled to increased cathepsin D activity.