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 language||English (US)|
|Number of pages||9|
|State||Published - 1991|
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