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The effect of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia. 1991

E Cersosimo, and P W Pisters, and G Pesola, and A Rogatko, and N A Vydelingum, and D Bajorunas, and M F Brennan
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, N.Y. 10021.

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.

UI MeSH Term Description Entries
D007262 Infusions, Intravenous The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it. Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D007328 Insulin A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1). Iletin,Insulin A Chain,Insulin B Chain,Insulin, Regular,Novolin,Sodium Insulin,Soluble Insulin,Chain, Insulin B,Insulin, Sodium,Insulin, Soluble,Regular Insulin
D007773 Lactates Salts or esters of LACTIC ACID containing the general formula CH3CHOHCOOR.
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D012039 Regional Blood Flow The flow of BLOOD through or around an organ or region of the body. Blood Flow, Regional,Blood Flows, Regional,Flow, Regional Blood,Flows, Regional Blood,Regional Blood Flows
D001786 Blood Glucose Glucose in blood. Blood Sugar,Glucose, Blood,Sugar, Blood
D002100 Cachexia General ill health, malnutrition, and weight loss, usually associated with chronic disease.

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