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 [3-3H] glucose infusion. The mean postabsorptive rate of glucose appearance in patients (2.9 +/- 0.1 mg/kg.min) was significantly higher (p less than 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 less than 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 less than 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.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021.
authors.forename: E
authors.initials: E
authors.lastname: Cersosimo
authors.forename: P W
authors.initials: PW
authors.lastname: Pisters
authors.forename: G
authors.initials: G
authors.lastname: Pesola
authors.forename: A
authors.initials: A
authors.lastname: Rogatko
authors.forename: N A
authors.initials: NA
authors.lastname: Vydelingum
authors.forename: D
authors.initials: D
authors.lastname: Bajorunas
authors.forename: M F
authors.initials: MF
authors.lastname: Brennan
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002100:Cachexia / Q000209:etiology / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage*; D007773:Lactates / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007773:Lactates