Insulin action on glucose and branched-chain amino acid metabolism in cancer cachexia: Differential effects of insulin Journal Article

Authors: Pisters, P. W. T.; Cersosimo, E.; Rogatko, A.; Brennan, M. F.
Article Title: Insulin action on glucose and branched-chain amino acid metabolism in cancer cachexia: Differential effects of insulin
Abstract: In addition to the maintenance of glucose homeostasis, insulin plays a major role in the regulation of branched-chain amino acid (BCAA) metabolism. We investigated insulin action on glucose turnover rates, arterial BCAA concentrations, and forearm BCAA flux in cancer cachexia. Six weight-losing patients with localized gastrointestinal malignancy and five age-matched control subjects underwent sequential 120-minute euglycemic insulin infusions. Steady-state insulin concentrations were 50 +/- 5, 97 +/- 14, and 435 +/- 14-mu-U/ml in patients and 44 +/- 4, 95 +/- 6, and 495 +/- 42-mu-U/ml in control subjects at the insulin infusion rates of 0.5, 1.0, and 4.0 mU/kg.min, respectively. During the 0.5 and 1.0 mU/kg.min insulin infusions, a primed, continuous infusion of D-[3-H-3] glucose was used to quantify endogenous glucose production. Total body glucose uptake was decreased in patients with cancer compared with control subjects at the 0.5 mU/kg . min (2.9 +/- 0.4 vs 3.6 +/- 1.2 mg/kg . min), 1.0 mU/kg . min (5.3 +/- 0.3 vs 8.7 +/- 0.8 mg/kg . min; p < 0.05), and 4.0 mU/kg . min (10.9 +/- 0.9 vs 13.7 +/- 1.1 mg/kg . min) insulin infusion rates, consistent with a state of insulin resistance. Progressive euglycemic insulin infusion induced a marked, comparable insulin-dependent decrease in arterial plasma BCAA concentrations in both patients with cancer and control subjects. There was no change in postabsorptive forearm BCAA flux with progressive hyperinsulinemia. Insulin-induced branched-chain hypoaminoacidemia is unimpaired in this group of patients manifesting resistance to insulin action on glucose metabolism, thereby providing evidence of a differential resistance to insulin action on glucose metabolism versus insulin action on BCAA concentrations in cancer cachexia. Peripheral BCAA flux is not affected by systemic insulin infusion, suggesting that skeletal muscle is not a major site of BCAA disposal during insulin-mediated hypoaminoacidemia.
Journal Title: Surgery
Volume: 111
Issue: 3
ISSN: 0039-6060
Publisher: Elsevier Inc.  
Date Published: 1992-03-01
Start Page: 301
End Page: 310
Language: English
ACCESSION: WOS:A1992HG78700010
PUBMED: 1542855
Notes: Article -- Source: Wos
Citation Impact
MSK Authors
  1. Murray F Brennan
    992 Brennan
  2. Peter W. T. Pisters
    21 Pisters
  3. Andre Rogatko
    22 Rogatko