Interaction of carnitine with insulin-stimulated glucose metabolism in humans.

To characterize the interactions of carnitine with glucose metabolism, we administered L-carnitine as a primed (3 mmol) constant (17 mumol/min) intravenous infusion to healthy young volunteers during short-term (2 h) euglycemic hyperinsulinemia. In comparison with a control (saline) infusion, exogenous carnitine administration resulted in a stable, fourfold increase in basal serum carnitine levels (160 +/- 14 vs. 36 +/- 2 microM, P less than 0.001). At similar steady-state plasma insulin levels (75 microU/ml), carnitine infusion was associated with a 17 +/- 3% stimulation of whole body glucose utilization (6.56 +/- 0.60 vs. 5.57 +/- 0.44 mg.min-1.kg-1, P less than 0.001). This effect was more pronounced in the subjects with higher rates of glucose disposal (r = 0.65, P less than 0.05). Net rates of insulin-induced glucose oxidation (measured by continuous, computerized indirect calorimetry) were similar with or without carnitine (1.67 +/- 0.23 vs. 1.65 +/- 0.10 mg.min-1.kg-1, respectively). As a consequence, the carnitine-induced enhancement of total glucose metabolism was quantitatively accounted for by a 50% increase in nonoxidative glucose disposal (2.89 +/- 0.81 vs. 1.92 +/- 0.51 mg.min-1.kg-1, P less than 0.05). The inhibitory effect of insulin on net lipid oxidation was not altered by carnitine (-0.67 +/- 0.09 vs. -0.62 +/- 0.06 mg.min-1.kg-1). Circulating levels of free fatty acids (FFA), glycerol, and beta-hydroxybutyrate fell in parallel during insulin infusion in the test and control study, and blood lactate concentrations rose by similar amounts (approximately 0.35 mM).(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  R. Bressler,et al.  THE EFFECT OF CARNITINE ON THE RATE OF INCORPORATION OF PRECURSORS INTO FATTY ACIDS. , 1965, The Journal of biological chemistry.

[2]  B. Crabtree,et al.  Flux-generating and regulatory steps in metabolic control , 1981 .

[3]  J. McGarry,et al.  Role of carnitine in hepatic ketogenesis. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[4]  C. Angelini,et al.  Carnitine Deficiency of Human Skeletal Muscle with Associated Lipid Storage Myopathy: A New Syndrome , 1973, Science.

[5]  J. McGarry,et al.  Ketogenesis and its regulation. , 1976, The American journal of medicine.

[6]  F. Nuttall,et al.  The glycogen synthase system in skeletal muscle of normal humans and patients with myotonic dystrophy: effect of glucose and insulin administration. , 1974, Metabolism: clinical and experimental.

[7]  J. Tobin,et al.  Effects of arterial versus venous sampling on analysis of glucose kinetics in man. , 1976, Journal of applied physiology.

[8]  R. DeFronzo,et al.  Effect of fatty acids on glucose production and utilization in man. , 1983, The Journal of clinical investigation.

[9]  C. Rebouche,et al.  Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport. , 1984, The Journal of clinical investigation.

[10]  W. Schenk,et al.  Carnitine levels in severe infection and starvation: a possible key to the prolonged catabolic state. , 1970, Surgery.

[11]  K. Frayn,et al.  Calculation of substrate oxidation rates in vivo from gaseous exchange. , 1983, Journal of applied physiology: respiratory, environmental and exercise physiology.

[12]  N L Jones,et al.  Evaluation of a microprocessor-controlled exercise testing system. , 1984, Journal of applied physiology: respiratory, environmental and exercise physiology.

[13]  R. DeFronzo,et al.  Regulation of Splanchnic and Peripheral Glucose Uptake by Insulin and Hyperglycemia in Man , 1983, Diabetes.

[14]  J. Bremer.  Carnitine--metabolism and functions. , 1983, Physiological reviews.

[15]  T. Bøhmer,et al.  CARNITINE DEFICIENCY INDUCED DURING INTERMITTENT HÆMODIALYSIS FOR RENAL FAILURE , 1978, The Lancet.

[16]  M. Ciman,et al.  EFFECT OF CARNITINE ON THE OXIDATION OF ALPHA-OXOGLUTARATE TO SUCCINATE IN THE PRESENCE OF ACETOACETATE OR PYRUVATE. , 1964, Biochimica et biophysica acta.

[17]  R. Steele,et al.  INFLUENCES OF GLUCOSE LOADING AND OF INJECTED INSULIN ON HEPATIC GLUCOSE OUTPUT * , 1959, Annals of the New York Academy of Sciences.

[18]  E. Newsholme,et al.  The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. , 1963, Lancet.

[19]  G. Fraenkel,et al.  Reversible enzymatic acetylation of carnitine. , 1955, Archives of biochemistry and biophysics.

[20]  S. Lindstedt,et al.  A method for the determination of carnitine in the picomole range. , 1972, Clinica chimica acta; international journal of clinical chemistry.

[21]  R. DeFronzo,et al.  The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization , 1981, Diabetes.

[22]  R. Bressler,et al.  THE ROLE OF CARNITINE IN ACETOACETATE PRODUCTION AND FATTY ACID SYNTHESIS. , 1965, The Journal of clinical investigation.

[23]  I. Fritz.  CARNITINE AND ITS ROLE IN FATTY ACID METABOLISM. , 1963, Advances in lipid research.

[24]  C Cobelli,et al.  Effect of insulin on the distribution and disposition of glucose in man. , 1985, The Journal of clinical investigation.

[25]  W. J. Brown,et al.  Systemic carnitine deficiency--a treatable inherited lipid-storage disease presenting as Reye's syndrome. , 1980, The New England journal of medicine.