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Protein anabolism is resistant to insulin action in lung cancer cachexia
Author(s) -
Winter Aaron,
Marliss Errol B.,
Baracos Vickie E.,
Chevalier Stéphanie
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.227.1
Subject(s) - endocrinology , medicine , cachexia , anabolism , hyperinsulinemia , insulin resistance , insulin , lung cancer , protein catabolism , weight loss , glucose clamp technique , chemistry , pancreatic hormone , cancer , obesity , amino acid , biochemistry
Cachexia is frequently observed in advanced non‐small cell lung cancer (NSCLC) and compromises functional status, response to treatment and survival. Inherent muscle loss could be due to a defective protein response to the main anabolic hormone, insulin. We assessed insulin resistance of whole body protein and glucose metabolism using the hyperinsulinemic, euglycemic, isoaminoacidemic clamp with 13 C‐leucine and 3 H‐glucose tracers, in 5 men with NSCLC (stage III‐IV) and 8 healthy weight‐stable men matched for age (67 ± 2 vs. 69 ± 1 yrs). In NSCLC, recent weight loss was 6.3 ± 0.9% and BMI (20.8 ± 1.3 vs. 25.1 ± 0.9 kg/m 2 ), body fat and fat‐free mass (FFM) were lower. Postabsorptive plasma glucose and insulin did not differ, but branched‐chain amino acid (BCAA) concentrations were lower. During hyperinsulinemia, glucose infusion rates did not differ between groups (4.4 ± 0.4 vs. 5.5 ± 0.7 mg/kg.min), indicating no further resistance beyond that conferred by aging. In contrast, AA infusion rates were markedly lower in NSCLC: 31.1 ± 2.5 vs. 39.9 ± 1.8 mg/min, adjusted for FFM and postabsorptive BCAAs (p=0.039). This could be due to impaired suppression of protein breakdown or stimulation of synthesis by insulin, or both, which will be determined from kinetic analyses. These preliminary results are consistent with a blunted protein anabolism and may help define optimal approaches to prevent muscle loss in cancer cachexia. (CIHR)