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

Eugenio Cersosimo, P. W T Pisters, G. Pesola, A. Rogatko, N. A. Vydelingum, D. Bajorunas, M. F. Brennan

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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 [3-3H] 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.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalSurgery
Volume109
Issue number4
StatePublished - 1991
Externally publishedYes

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Cachexia
Lactic Acid
Insulin
Glucose
Neoplasms
Hyperinsulinism
Weights and Measures
Glucose Clamp Technique
Forearm
Insulin Resistance
Healthy Volunteers

ASJC Scopus subject areas

  • Surgery

Cite this

Cersosimo, E., Pisters, P. W. T., Pesola, G., Rogatko, A., Vydelingum, N. A., Bajorunas, D., & Brennan, M. F. (1991). The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. Surgery, 109(4), 459-467.

The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. / Cersosimo, Eugenio; Pisters, P. W T; Pesola, G.; Rogatko, A.; Vydelingum, N. A.; Bajorunas, D.; Brennan, M. F.

In: Surgery, Vol. 109, No. 4, 1991, p. 459-467.

Research output: Contribution to journalArticle

Cersosimo, E, Pisters, PWT, Pesola, G, Rogatko, A, Vydelingum, NA, Bajorunas, D & Brennan, MF 1991, 'The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia', Surgery, vol. 109, no. 4, pp. 459-467.
Cersosimo E, Pisters PWT, Pesola G, Rogatko A, Vydelingum NA, Bajorunas D et al. The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. Surgery. 1991;109(4):459-467.
Cersosimo, Eugenio ; Pisters, P. W T ; Pesola, G. ; Rogatko, A. ; Vydelingum, N. A. ; Bajorunas, D. ; Brennan, M. F. / The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. In: Surgery. 1991 ; Vol. 109, No. 4. pp. 459-467.
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