Metabolic effects of oral glucose in the liver of fasted rats.

Twenty-four-hour-fasted rats were given glucose (4 g/kg) by gavage. Glucose absorption and portal and peripheral plasma glucose, lactate, and insulin concentrations, as well as liver glucose, UDPglucose, glucose-6-P, lactate, ATP, and inorganic phosphate (Pi), and % glycogen synthase I and % phosphorylase a were measured at 10, 20, 30, 40, 60, and 120 min after the glucose was given. Liver and muscle glycogen also were measured. Ninety-one percent of the glucose load had disappeared from the gut in 2 h. Despite increased plasma glucose and insulin levels the liver continued to produce glucose. Lactate produced in the periphery was the major substrate for gluconeogenesis, and lactate utilization could account for the hepatic glycogen synthesized. Glucose ingestion did not affect lactate production by the splanchnic bed. In the liver glucose-6-P was transiently increased; UDP glucose decreased after glucose administration. ATP and Pi were unchanged. Glycogen synthase was activated by 20 min without a significant change in phosphorylase a. Hepatic glycogen increased linearly after 20 min. Total glucose storage as glycogen was similar in liver (20%) and muscle (19%). We could account for 41% of the glucose absorbed as glycogen, unmetabolized glucose, or glucose metabolites. Most of the remainder probably was oxidized.

[1]  A. N. Wick,et al.  The Metabolism of Fructose by the Extrahepatic Tissues , 1953, Diabetes.

[2]  J. Huttunen Fructose in medicine , 1971, Postgraduate medical journal.

[3]  K. Alberti,et al.  Dangers of intravenous fructose. , 1972, Lancet.

[4]  W. Huckabee,et al.  Control of concentration gradients of pyruvate and lactate across cell membranes in blood. , 1956, Journal of applied physiology.

[5]  W. Waldhäusl,et al.  Insulin production rate, hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus , 1982, Diabetologia.

[6]  F. Nuttall,et al.  Stimulation of liver glycogen particle synthase D phosphatase activity by caffeine, AMP, and glucose 6-phosphate. , 1982, Archives of biochemistry and biophysics.

[7]  H. Krebs,et al.  The cause of hepatic accumulation of fructose 1-phosphate on fructose loading. , 1970, The Biochemical journal.

[8]  R. DeFronzo,et al.  The effect of hyperglycemia, hyperinsulinemia, and route of glucose administration on glucose oxidation and glucose storage. , 1982, Metabolism: clinical and experimental.

[9]  A. W. Tan Presence of an intermediate synthase form during the conversion of glycogen synthase D into synthase I in rat liver extract. , 1981, The Biochemical journal.

[10]  C. H. Fiske,et al.  THE COLORIMETRIC DETERMINATION OF PHOSPHORUS , 1925 .

[11]  T. Brody,et al.  PHOSPHORYLASE ACTIVITY IN RAT LIVER AND SKELETAL MUSCLE AFTER CATECHOLAMINES. , 1963, Biochemical pharmacology.

[12]  A. Dawson,et al.  Absorption of Fructose in Man , 1965, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[13]  J. Radziuk,et al.  The Effects of Ingested and Intravenous Glucose on Forearm Uptake of Glucose and Glucogenic Substrate in Normal Man , 1983, Diabetes.

[14]  D. Kipnis,et al.  Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. , 1967, The Journal of clinical investigation.

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

[16]  E. Taylor,et al.  Glycogen synthesis in the perfused liver of the starved rat. , 1971, The Biochemical journal.

[17]  F. Smith,et al.  Colorimetric Method for Determination of Sugars and Related Substances , 1956 .

[18]  F. Nuttall,et al.  Glycogen Synthase, Synthase Phosphatase, and Phosphorylase Response to Glucose in Somatostatin-Pretreated Intact Rats , 1979, Diabetes.

[19]  R. DeFronzo,et al.  Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[20]  I. Chaikoff,et al.  On the manner of transport of absorbed fructose. , 1957, The Journal of biological chemistry.

[21]  T. B. Miller Cyclic AMP-mediated activation of hepatic glycogenolysis by fructose. , 1978, Biochimica et biophysica acta.

[22]  R. Crane Intestinal absorption of sugars. , 1960, Physiological reviews.

[23]  A. W. Tan A simplified method for the preparation of pure UDP[14C] glucose. , 1979, Biochimica et biophysica acta.

[24]  S. Weinhouse,et al.  Dietary and hormonal effects on gluconeogenesis in the rat. , 1965, The Journal of biological chemistry.

[25]  W. Glinsmann,et al.  Control of rat liver glycogen synthetase and phosphorylase activities by glucose. , 1970, Biochemical and biophysical research communications.

[26]  P. Felig,et al.  Influence of Oral Glucose Ingestion on Splanchnic Glucose and Gluconeogenic Substrate Metabolism in Man , 1975, Diabetes.

[27]  C. Cori THE FATE OF SUGAR IN THE ANIMAL BODY III. THE RATE OF GLYCOGEN FORMATION IN THE LIVER OF NORMAL AND INSULINIZED RATS DURING THE ABSORPTION OF GLUCOSE, FRUCTOSE, AND GALACTOSE , 1926 .

[28]  J. A. Thomas,et al.  A rapid filter paper assay for UDPglucose-glycogen glucosyltransferase, including an improved biosynthesis of UDP-14C-glucose. , 1968, Analytical biochemistry.

[29]  J. Exton,et al.  Studies on the alpha-adrenergic activation of hepatic glucose output. I. Studies on the alpha-adrenergic activation of phosphorylase and gluconeogenesis and inactivation of glycogen synthase in isolated rat liver parenchymal cells. , 1976, The Journal of biological chemistry.

[30]  O. H. Lowry,et al.  Effect of fructose, dihydroxyacetone, glycerol, and glucose on metabolites and related compounds in liver and kidney. , 1970, The Journal of biological chemistry.

[31]  E. Jéquier,et al.  Relationship between glucose oxidation and glucose tolerance in man. , 1982, Metabolism: clinical and experimental.

[32]  H. Hers,et al.  The mechanism of adenosine triphosphate depletion in the liver after a load of fructose. A kinetic study of liver adenylate deaminase. , 1977, The Biochemical journal.

[33]  R. A. Jackson,et al.  Dietary Diabetes: The Influence of a Low Carbohydrate Diet on Forearm Metabolism in Man , 1973, Diabetes.

[34]  P. Björntorp,et al.  Effects of feeding states on lipid radioactivity in liver, muscle and adipose tissue after injection of labelled glucose in the rat. , 1970, Acta physiologica Scandinavica.

[35]  F. Nuttall,et al.  The regulation of liver glycogen synthetase D phosphatase by ATP and glucose. , 1973, Biochemical and biophysical research communications.

[36]  K. Zierler,et al.  Forearm metabolism in obesity and its response to intra-arterial insulin. Characterization of insulin resistance and evidence for adaptive hyperinsulinism. , 1962, The Journal of clinical investigation.

[37]  F. Nuttall,et al.  Characteristics of the dephosphorylated form of phosphorylase purified from rat liver and measurement of its activity in crude liver preparations. , 1975, Biochimica et biophysica acta.

[38]  P. Richardson,et al.  Liver blood flow. I. Intrinsic and nervous control of liver blood flow. , 1981, Gastroenterology.

[39]  H. Hers,et al.  Mechanism of activation of glycogen phosphorylase by fructose in the liver. Stimulation of phosphorylase kinase related to the consumption of adenosine triphosphate. , 1979, The Biochemical journal.

[40]  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.

[41]  J. A. Moorhouse,et al.  Fructose and diabetes. , 1957, The American journal of medicine.

[42]  F. Nuttall,et al.  Radioactive method for the assay of glycogen phosphorylases. , 1972, Analytical biochemistry.

[43]  L. Sestoft,et al.  Determination of the kinetic constants of fructose transport and phosphorylation in the perfused rat liver. , 1974, Biochimica et biophysica acta.

[44]  E. Froesch,et al.  Inhibition of Phosphorylase‐a by Fructose‐1‐Phosphate, α‐Glycerophosphate and Fructose‐1,6‐Diphosphate: Explanation for Fructose‐Induced Hypoglycaemia in Hereditary Fructose Intolerance and Fructose‐1,6‐Diphosphatase Deficiency * , 1973, European journal of clinical investigation.

[45]  G. Wilkinson,et al.  Effects of alteration of hepatic microsomal enzyme activity on liver blood flow in the rat. , 1976, Biochemical pharmacology.

[46]  D. Topping,et al.  The concentration of fructose, glucose and lactate in the splanchnic blood vessels of rats absorbing fructose. , 1971, Nutrition and metabolism.