Exogenous Glucose Oxidation Research Articles

Glucose utilization during exercise in normal and diabetic subjects. The role of insulin.

Due to selective isotopic effects occurring during photosynthesis, certain natural sugars are enriched in 13C Using such “naturally labeled 13C-glucose,” we studied glucose oxidation during exercise in seven normal volunteers and in six insulin-dependent diabetics after an overnight fast. In the diabetics, blood glucose was monitored the night before the test and adjusted to about 100 mg/dl by intravenous insulin infusion. The insulin infusion was withheld 15 min before exercise in four diabetics and maintained at 0.9 U/h for 2 h; then it was maintained at 0.6 U/h for 2 h in five diabetics. Three patients underwent both tests. All subjects exercised on a treadmill for 4 h at about 45% of their max. After 15 min adaptation, all received 100 g 13C-labeled glucose orally. Total glucose oxidation was derived from non-protein RQ and exogenous glucose oxidation evaluated as previously described. The diabetics had no residual B-cell function as indicated by negligible plasma C-peptide values and a lack of Cpeptide response to the oral glucose challenge. Total glucose oxidation averaged 230 ± 14 g/4 h in the normal subjects. It was similar (238 ± 19 g/4 h) in the diabetics receiving an intravenous insulin infusion, but decreased to 176 ± 14 g/4 h when no insulin was infused. Exogenous glucose oxidation was 92 ± 3 g/4 h and 84 ± 8 g/4 h (not statistically different) in the controls and in the insulin-infused diabetics, respectively. It was 43 ± 11 g/4 h in the diabetics exercising without being infused with insulin. We conclude that (1) in well-insulinized diabetic patients, prolonged muscular exercise can be performed under metabolic conditions which are basically similar to those of normal subjects; (2) during prolonged exercise, well-insulinized diabetic patients are able to oxidize up to 85–90% of a 100-g exogenous glucose load given orally and oral glucose can thus be ingested during prolonged exercise in well-controlled juvenile insulintreated diabetics; (3) even in the absence of insulin administration during exercise, juvenile diabetics who start exercising when blood glucose is near normal are able to perform a 4-h exercise at 45–50% of their max. Under these conditions, however, they are unable to utilize more than 40–45% of a 100-g glucose load given orally. They rely more upon lipid stores than the normal subjects or the well-insulinized diabetics.

Glucose oxidation in relation to the size of the oral glucose loading dose

Using “naturally labeled 13C-glucose” the conversion to expired air CO 2 of 100, 66 and 33 g oral glucose loads was evaluated, during 7 hr, in 6 male healthy volunteers. The total amounts of exogenous glucose converted to expired air CO 2 were proportional to the loading doses and averaged, in g/7 hr, 14.6 ± 2.1 for 33 g, 20.8 ± 2.1 for 66 g and 31.2 ± 1.6 for 100 g. In contrast total glucose oxidation, evaluated by indirect calorimetry, was similar in the three groups and was not correlated with the dose of glucose given. The plasma insulin response was significantly correlated with the load of glucose ( r = 0.86; p < 0.001) whereas such correlation was not observed with the blood glucose response. Comparison with data available in the literature on the influence of the size of the oral glucose load on endogenous glucose production and on splanchnic glucose output suggests that the greater oxidation of exogenous glucose seen when the oral load of glucose is increased essentially results from a greater enrichment of the systemic glucose pool with exogenous glucose.

Concanavalin A-induced chemiluminescence in rat thymus lymphocytes. Its origin and role in mitogenesis.

1. The luminol-dependent chemiluminescence of rat thymocytes responding to concanavalin A can be resolved into glucose-dependent and glucose-independent portions. 2. The glucose-dependent portion, supported by D-glucose and D-mannose oxidation, is inhibited by catalase (200 microgram/ml), amobarbital (1 mM) and hexose analogues that block D-glucose uptake. Thus concanavalin A may activate, transiently, an NAD(P)H oxidase that utilizes reducing equivalents derived from the oxidation of exogenous glucose to give dismutation products of O2- (including H2O2) as its major products. 3. The glucose-independent portion is inhibited by eicosa-5,8,11,14-tetraynoic acid but not by indomethacin. It may therefore be associated with the conversion of hydroperoxy intermediates of arachidonic acid metabolism to hydroxy products by the lipoxygenase pathway. 4. Preincubation of thymocytes for 18 h in serum-free medium enhances the subsequent chemiluminescent response to concanavalin A severalfold and evokes the response at a lower threshold concentration. The incorporation of [3H]thymidine by preincubated cells is similarly enhanced at low doses of concanavalin A, whereas the response to optimal doses is unaltered. 5. Catalase does not inhibit the enhanced incorporation of [3H]thymidine obtained in response to concanavalin A, but instead amplifies the response to low doses in the same manner as preincubation.

Oxidation of an exogenous glucose load using naturally labelled 13C-glucose. Effect of butylbiguanide therapy in obese mildly diabetic subjects.

The effect of a 14 day-administration of butylbiguanide was investigated in a group of 10 obese patients with mild-to-moderate glucose intolerance. Glucose tolerance was significantly improved, while fasting blood glucose and plasma levels of free fatty acids, insulin and glucagon remained unchanged. The estimation of the amount of the oral glucose load oxidized into CO2 was performed by means of a recently described procedure using "naturally labelled 13C-glucose" as tracer. The curves depicting the oxidation of the exogenous glucose load were similar in shape and magnitude before and after administration of the biguanide; in the latter case, however, slightly higher rates of oxidation of exogenous glucose were recorded during the 2nd, 3rd and 4th hours of the test. These data do not provide evidence that the biguanide-induced improvement in glucose tolerance in patients with mild-to-moderate glucose intolerance is associated with any inhibiting or delaying effect of this type of drug on intestinal absorption (and subsequent oxidation) of the exogenous glucose load. On the contrary, a slight, but statistically significant, increase in the oxidation of exogenous glucose has been observed after butylbiguanide.

Effect of pH, pCO 2 and bicarbonate on metabolism of glucose by perfused rat heart

1. 1. Effects of pH, pCO 2 and bicarbonate on metabolism of [ 14C 6]glucose in the isolated perfused rat heart were studied. 2. 2. With an alkaline extracellular pH, glucose uptake, lactate production and glycogen breakdown increased, and oxidation of exogenous glucose remained constant. These findings are compatible with enhancement of phosphofructokinase (EC 2.7.1.11) activity. 3. 3. At an acid extracellular pH, glucose uptake and lactate production decreased, glycogen levels were unchanged, and 14CO 2 production was unchanged until pH fell below 7.0, at which time 14CO 2 decreased. 4. 4. Glucose uptake, lactate production, 14CO 2 production and glycogen levels were similar in hearts perfused at pH 7.50 with either a bicarbonate buffer or 30 mM Tris.

Evidence for the Widespread Occurrence of Induced Respiration in Slices of Plant Tissues

Thin slices of a wide range of plant tissues developed increased rates of respiration when incubated in aerated distilled water at 26�0 for 24 hr. The increased respiration of slices of the flesh of pumpkin (Oucurbita pepo L.) fruit and celery (Apium graveolens L.) petiole was shown to resemble the induced respimtion of slices of underground storage organs. The increase in respiration rate was largely prevented in pumpkin and celery slices when they were incubated at 2�0, or in the absence of oxygen, or in chloramphenicol, or in 5-fluorouracil. In the same tissues the increased respiration was shown to be accompanied by marked increases in the rates of uptake and oxidation of exogenous glucose and by a lowering of the initial 0 6/01 ratios.

Metabolism of Sarcina lutea: III. Endogenous metabolism

Sarcina lutea, harvested from peptone media, displays a high rate of endogenous metabolism which may be diminished to a negligible level by aeration of cell suspensions at 37°. During the process, ammonia appears in the supernatant fluid and the free amino acid pool decreases by approximately one half, remaining constant when the metabolism has fallen to negligible proportions; there is no concomitant decrease in either cell carbohydrate or fat. The ultracentrifugal pattern of cell extracts does not change significantly during diminution of endogenous metabolism and the observed oxygen consumption can be accounted for solely by the oxidation of amino acids and peptides within the pool. Endogenous metabolism is restored by the incubation of cell suspensions with casein hydrolysate, glucose plus ammonium salt and glucose alone, in that order of decreasing effectiveness. In each case there is a good correlation between the increase in Q 02 and the increase in the free amino acid-pool concentration; the increase of the pool when cells are incubated with glucose alone is attributed to the mobilization of some endogenous peptide or protein material. The pattern of the amino acid pool has been investigated chromatographically during the diminution and restoration of endogenous metabolism. It is concluded that amino acids are the substrates for endogenous metabolism. Incubation with glucose produces extensive intracellular carbohydrate deposition whereas incubation with casein hydrolysate is without effect on the carbohydrate content of the cells. High levels of endogenous metabolism and the oxidation of exogenous glucose are mutually inhibitory.

Silicon metabolism in diatoms. III. Respiration and silicon uptake in Navicula pelliculosa.

1. Evidence is presented that silicon uptake in the diatom Navicula pelliculosa is linked with aerobic respiration. 2. Cyanide, fluoride, iodoacetate, arsenite, azide, and fluoroacetate, at concentrations inhibitory to respiration, were also inhibitory to silicon uptake. 3. 2,4-Dinitrophenol (1 to 2 x 10(-5)M) stimulated respiration by 100 per cent, but almost completely inhibited silicon uptake. 4. The respiratory quotient of non-Si-deficient cells decreased from 0.93 to 0.75 after 4 days of starvation in darkness. Glucose (1 per cent) raised the respiratory quotient of such starved cells to 1.05. 5. Silicate (20 mg. Si/liter) stimulated respiration of unstarved Si-deficient cells by about 40 per cent. The effect of silicate on the respiration of Si-deficient cells which had been starved in darkness for 4 days was less marked. 6. The respiratory quotient of Si-deficient cells decreased from 0.8-0.9 to 0.3 after 4 days of starvation in darkness. The addition of silicate to starved cells raised the quotient to 0.5. This represented a 25 per cent stimulation of oxygen uptake concomitant with a 90 per cent stimulation of carbon dioxide evolution. 7. Glucose (1 per cent) caused an increase of respiratory quotient in starved cells from 0.3 to 0.7-0.8. The addition of silicate had no effect on the R.Q. during the oxidation of exogenous glucose. 8. Substrates (glucose, fructose, galactose, lactate, succinate, citrate, glycerol), which caused a stimulation of respiration in starved cells, also stimulated silicon uptake by those cells. However, the stimulation of silicon uptake (50 to 100 per cent) was not proportional to the respiratory stimulation by these substrates (30 to 300 per cent).