Protein metabolism and insulin resistance in non-small cell lung cancer cachexia.

摘要

Cancer cachexia is characterized by weight loss and insulin resistance. Previous work has shown blunted protein anabolism in insulin resistant conditions. This study tested whether hyperaminoacidemia with hyperinsulinemia elicits blunted whole-body protein anabolism in cachectic non-small cell lung cancer (NSCLC). Whole-body [13C]leucine and [3H]glucose kinetics were assessed in 8 NSCLC patients and 10 age and weight-matched controls during a euglycemic, hyperinsulinemic, clamp with isoaminoacidemia (Iso-AA), followed by hyperaminoacidemia (Hyper-AA). Glucose utilization increased from Iso-AA to Hyper-AA but was lower in NSCLC patients. During Iso-AA, protein breakdown decreased and synthesis was unchanged resulting in positive net balance that was lower in NSCLC patients. During Hyper-AA, synthesis increased but breakdown was unchanged resulting in increased net balance in both groups. In summary, weight-losing NSCLC patients demonstrate insulin resistance of whole-body glucose and protein metabolism. Physiologic hyperaminoacidemia normalized their anabolic response to that of controls and did not impair insulin sensitivity of glucose.