Insulin regulation of renal glucose metabolism in humans.

Eighteen healthy subjects had arterialized hand and renal veins catheterized after an overnight fast. Systemic and renal glucose and glycerol kinetics were measured with [6,6-2H2]glucose and [2-13C]glycerol before and after 180-min peripheral infusions of insulin at 0.125 (LO) or 0.25 (HI) mU ⋅ kg-1 ⋅ min-1with variable [6,6-2H2]dextrose or saline (control). Renal plasma flow was determined by plasma p-aminohippurate clearance. Arterial insulin increased from 37 ± 8 to 53 ± 5 (LO) and to 102 ± 10 pM (HI, P < 0.01) but not in control (35 ± 8 pM). Arterial glucose did not change and averaged 5.2 ± 0.1 (control), 4.7 ± 0.2 (LO), and 5.1 ± 0.2 (HI) μmol/ml; renal vein glucose decreased from 4.8 ± 0.2 to 4.5 ± 0.2 μmol/ml (LO) and from 5.3 ± 0.2 to 4.9 ± 0.1 μmol/ml (HI) with insulin but not saline infusion (5.3 ± 0.1 μmol/ml). Endogenous glucose production decreased from 9.9 ± 0.7 to 6.9 ± 0.5 (LO) and to 5.7 ± 0.5 (HI) μmol ⋅ kg-1 ⋅ min-1; renal glucose production decreased from 2.5 ± 0.6 to 1.5 ± 0.5 (LO) and to 1.2 ± 0.6 (HI) μmol ⋅ kg-1 ⋅ min-1, whereas renal glucose utilization increased from 1.5 ± 0.6 to 2.6 ± 0.7 (LO) and to 2.9 ± 0.7 (HI) μmol ⋅ kg-1 ⋅ min-1after insulin infusion (all P < 0.05 vs. baseline). Neither endogenous glucose production (10.0 ± 0.4), renal glucose production (1.1 ± 0.4), nor renal glucose utilization (0.8 ± 0.4) changed in the control group. During insulin infusion, systemic gluconeogenesis from glycerol decreased from 0.67 ± 0.05 to 0.18 ± 0.02 (LO) and from 0.60 ± 0.04 to 0.20 ± 0.02 (HI) μmol ⋅ kg-1 ⋅ min-1( P < 0.01), and renal gluconeogenesis from glycerol decreased from 0.10 ± 0.02 to 0.02 ± 0.02 (LO) and from 0.15 ± 0.03 to 0.09 ± 0.03 (HI) μmol ⋅ kg-1 ⋅ min-1( P < 0.05). In contrast, during saline infusion, systemic (0.66 ± 0.03 vs. 0.82 ± 0.05 μmol ⋅ kg-1 ⋅ min-1) and renal gluconeogenesis from glycerol (0.11 ± 0.02 vs. 0.41 ± 0.04 μmol ⋅ kg-1 ⋅ min-1) increased ( P < 0.05 vs. baseline). We conclude that glucose production and utilization by the kidney are important insulin-responsive components of glucose metabolism in humans.

[1]  N. Abumrad,et al.  Renal lactate metabolism and gluconeogenesis during insulin-induced hypoglycemia. , 1998, Diabetes.

[2]  C Meyer,et al.  Human kidney free fatty acid and glucose uptake: evidence for a renal glucose-fatty acid cycle. , 1997, The American journal of physiology.

[3]  N. Abumrad,et al.  Renal Glucose Production During Insulin-Induced Hypoglycemia , 1997, Diabetes.

[4]  J. Miles,et al.  Effects of pulsatile delivery of basal growth hormone on lipolysis in humans. , 1996, The American journal of physiology.

[5]  B. Zinman,et al.  Hepatic Glucose Production Is Regulated Both by Direct Hepatic and Extrahepatic Effects of Insulin in Humans , 1996, Diabetes.

[6]  R. Minshall,et al.  Kininase II-Type Enzymes: Their Putative Role in Muscle Energy Metabolism , 1996, Diabetes.

[7]  M. Stumvoll,et al.  Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine. , 1995, The Journal of clinical investigation.

[8]  R. Judd,et al.  Insulin regulation of renal glucose metabolism in conscious dogs. , 1994, The Journal of clinical investigation.

[9]  J. F. Burke,et al.  Determination of the isotope enrichment of one or a mixture of two stable labelled tracers of the same compound using the complete isotopomer distribution of an ion fragment; theory and application to in vivo human tracer studies. , 1993, Biological mass spectrometry.

[10]  P. Sauer,et al.  Glucose Kinetics and Glucoregulatory Hormone Levels in Ventilated Preterm Infants on the First Day of Life , 1993, Pediatric Research.

[11]  C. Cobelli,et al.  Methods for assessment of the rate of onset and offset of insulin action during nonsteady state in humans. , 1993, The American journal of physiology.

[12]  C Cobelli,et al.  Hepatic and extrahepatic insulin action in humans: measurement in the absence of non-steady-state error. , 1993, The American journal of physiology.

[13]  P. Pisters,et al.  The effects of euglycemic hyperinsulinemia and amino acid infusion on regional and whole body glucose disposal in man. , 1991, Metabolism: clinical and experimental.

[14]  R. Bergman,et al.  Peripheral effects of insulin dominate suppression of fasting hepatic glucose production. , 1990, The American journal of physiology.

[15]  R. Wolfe,et al.  The relationship between gluconeogenic substrate supply and glucose production in humans. , 1990, The American journal of physiology.

[16]  R. Rizza,et al.  Assessment of the postprandial pattern of glucose metabolism in nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus using a simultaneous infusion of [2(3)H] and [3(3)H] glucose. , 1989, Metabolism: clinical and experimental.

[17]  R. Bergman,et al.  Modeling Error and Apparent Isotope Discrimination Confound Estimation of Endogenous Glucose Production During Euglycemic Glucose Clamps , 1988, Diabetes.

[18]  J. Revkin,et al.  An isotopic method for measurement of muscle protein synthesis and degradation in vivo. , 1987, The Biochemical journal.

[19]  B. Beaufrère,et al.  Determination of steady state and nonsteady-state glycerol kinetics in humans using deuterium-labeled tracer. , 1987, Journal of lipid research.

[20]  M. Jensen,et al.  Lipolysis during fasting. Decreased suppression by insulin and increased stimulation by epinephrine. , 1987, The Journal of clinical investigation.

[21]  W. Guder,et al.  Renal substrate metabolism. , 1986, Physiological reviews.

[22]  M. Vranic,et al.  Minimal Increases in Glucagon Levels Enhance Glucose Production in Man with Partial Hypoinsulinemia , 1983, Diabetes.

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

[24]  E. Baráth,et al.  Fundamentals of Biostatistics. , 1992 .

[25]  R. Sherwin,et al.  Synergistic interactions among antiinsulin hormones in the pathogenesis of stress hyperglycemia in humans. , 1981, The Journal of clinical endocrinology and metabolism.

[26]  G. Shulman,et al.  Differential Time Course of Glucagon's Effect on Glycogenolysis and Gluconeogenesis in the Conscious Dog , 1981, Diabetes.

[27]  B. Sobel,et al.  An improved assay with 4-(2-thiazolylazo)-resorcinol for non-esterified fatty acids in biological fluids. , 1980, Clinica chimica acta; international journal of clinical chemistry.

[28]  R. Rizza,et al.  Adrenergic mechanisms for the effects of epinephrine on glucose production and clearance in man. , 1980, The Journal of clinical investigation.

[29]  R. DeFronzo,et al.  The effects of glucose and insulin on renal electrolyte transport. , 1976, The Journal of clinical investigation.

[30]  R. DeFronzo,et al.  The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. , 1975, The Journal of clinical investigation.

[31]  P. Felig,et al.  Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. , 1974, The Journal of clinical investigation.

[32]  D. Steinberg,et al.  Effect of Sodium Linoleate Infusion on Plasma Free Fatty Acids, Glucose, Insulin, and Ketones in Unanesthetized Dogs , 1972, Diabetes.

[33]  E. Cerasi,et al.  Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus. , 1972, The Journal of clinical investigation.

[34]  Fuel of respiration of outer renal medulla. , 1971, The American journal of physiology.

[35]  G F Cahill,et al.  Starvation in man. , 1970, The New England journal of medicine.

[36]  H. Krebs,et al.  The fuel of respiration of rat kidney cortex. , 1969, The Biochemical journal.

[37]  G F Cahill,et al.  Amino acid metabolism during prolonged starvation. , 1969, The Journal of clinical investigation.

[38]  P. Felig,et al.  Liver and kidney metabolism during prolonged starvation. , 1969, The Journal of clinical investigation.

[39]  D. Kipnis,et al.  Hormone-fuel interrelationships during fasting. , 1966, The Journal of clinical investigation.

[40]  M. West,et al.  Ultrastructural observations on renal glycogen in normal and pathologic human kidneys. , 1966, Laboratory investigation; a journal of technical methods and pathology.

[41]  V. Herbert,et al.  Coated charcoal immunoassay of insulin. , 1965, The Journal of clinical endocrinology and metabolism.

[42]  E. Newsholme,et al.  Regulation of glucose uptake by muscle. 8. Effects of fatty acids, ketone bodies and pyruvate, and of alloxan-diabetes and starvation, on the uptake and metabolic fate of glucose in rat heart and diaphragm muscles. , 1964, The Biochemical journal.

[43]  H. Krebs,et al.  RENAL GLUCONEOGENESIS. IV. GLUCONEOGENESIS FROM SUBSTRATE COMBINATIONS. , 1963, Acta biologica et medica Germanica.

[44]  C. Brun.  A rapid method for the determination of para-aminohippuric acid in kidney function tests. , 1951, The Journal of laboratory and clinical medicine.