Normal protein anabolic response to hyperaminoacidemia in insulin‐resistant patients with lung cancer cachexia

Abstract

Insulin resistance is thought to underlie muscle wasting in cancer cachexia. Objective: to test whether insulin resistance is present in cachectic lung cancer patients and if a physiological elevation of amino acids (AA) with hyperinsulinemia would compensate for it. Whole-body 13C-leucine and 3H-glucose kinetics were assessed in 9 non-small cell lung cancer (NSCLC) and 9 healthy men matched for BMI, age and smoking during a euglycemic, hyperinsulinemic, isoaminoacidemic (IsoAA) followed by hyperaminoacidemic clamp (HyperAA). Fasting glucose and protein kinetics were similar. Glucose uptake increased in both from IsoAA to HyperAA and was significantly lower in NSCLC patients during both states. During IsoAA, protein breakdown was suppressed and synthesis did not change in both but the increase in net anabolism (synthesis-breakdown) was less in NSCLC (p=0.004); AA infusion was accordingly lower. In HyperAA, synthesis increased with no further change in breakdown, resulting in the same increase in net anabolism and AA infusion in both. NSCLC patients with moderate cachexia showed severe insulin resistance of glucose but milder resistance of protein anabolism. Their anabolic protein response was stimulated normally by HyperAA (which did not worsen insulin sensitivity of glucose). Thus, ample provision of AA is a testable strategy to overcome the protein anabolic failure of cancer cachexia. (Funded by CIHR)