The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia Journal Article


Authors: Cersosimo, E.; Pisters, P. W. T.; Pesola, G.; Rogatko, A.; Vydelingum, N. A.; Bajorunas, D.; Brennan, M. F.
Article Title: The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia
Abstract: With the euglycemic clamp technique, we evaluated the effects of graded doses of insulin on glucose turnover rates and forearm lactate balance in five weight-losing patients with cancer before surgery and five age- and weight-matched healthy volunteers (control subjects). Insulin was infused sequentially at increasing rates of 0.5 (low physiologic), 1.0 (high physiologic), and 4.0 (supraphysiologic) mU/kg.min for 120 minutes each. Concurrently, rates of glucose appearance and disappearance were derived from [3-H-3] glucose infusion. The mean postabsorptive rate of glucose appearance in patients (2.9 +/- 0.1 mg/kg . min) was significantly higher (p < 0.02) than that of control subjects (1.98 +/- 0.16 mg/kg . min). Complete suppression of endogenous glucose production occurred at high physiologic insulin concentrations. With progressive insulin infusion, the rate of glucose disappearance increased to 3.6 +/- 1.2, 8.7 +/- 0.8, and 13.7 +/- 1.1 mg/kg/min in control subjects and 2.9 +/- 0.4, 5.3 +/- 0.3, and 10.9 +/- 0.9 mg/kg . min in patients, significantly different from that of control subjects (p < 0.05) during the intermediate (high physiologic) insulin infusion. A comparable slight increase in arterial plasma lactate concentration was observed in both groups with progressive hyperinsulinemia. Baseline peripheral lactate flux was identical in patients (-272 +/- 56 nmol/100 gm . min) and in controls (-271 +/- 57 nmol/100 gm . min). Progressive physiologic hyperinsulinemia resulted in significantly (p < 0.05) augmented peripheral lactate efflux in patients (-824 +/- 181 nmol/100 gm . min) compared with control subjects (-287 +/- 64 nmol/100 gm . min). Supraphysiologic insulin abolished this increased lactate efflux in patients. Postabsorptive rates of endogenous glucose appearance in weight-losing patients with cancer were elevated, but complete suppression was achieved with insulin concentrations in the physiologic range. Total body glucose use was diminished in these patients, consistent with a state of insulin resistance. This impaired insulin action on peripheral glucose use was associated with an increase in peripheral lactate release in patients.
Keywords: resistance; muscle; patient; colorectal-cancer; hyperinsulinemia; total parenteral-nutrition; turnover; metabolic response; lactic-acidosis; weight-losing cancer
Journal Title: Surgery
Volume: 109
Issue: 4
ISSN: 0039-6060
Publisher: Elsevier Inc.  
Date Published: 1991-04-01
Start Page: 459
End Page: 467
Language: English
ACCESSION: WOS:A1991FF16600003
PROVIDER: wos
PUBMED: 2008651
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
  4. Gene R. Pesola
    16 Pesola