Glucose Recycling Research Articles

Abnormal Erythrocyte Metabolism in Hepatic Disease

Erythrocyte (RBC) metabolic studies were done on 114 patients with severe hepatic disease. Heinz body formation after incubation of RBCs with acetyl phenylhydrazine was found to be significantly higher in patients than in controls. RBC-reduced glutathione levels were lower than those of controls both before and after incubation with acetyl phenylhydrazine, and patients with the highest Heinz body counts had the lowest reduced glutathione levels. RBC methylene blue-stimulated hexose monophosphate (HMP) shunt metabolism and glucose recycling through the shunt were significantly lower in patients with active hepatic disease than in controls. There was no difference in resting HMP shunt activity or in resting recycling of glucose. Despite impairment of shunt metabolism, total glucose consumption was greater in patients than in controls. The patients with the lowest stimulated HMP shunt metabolism and glucose recycling had the highest Heinz body counts, lowest reduced glutathione, and highest total glucose consumption. A continuum of abnormal shunt metabolism was seen, from a mild reduction of stimulated HMP shunt activity to a severe combined decrease in both the HMP shunt and glucose recycling. When measured, glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and transketolase were normal or increased. Sequential studies were done on 11 patients who had abnormal metabolic studies. Coincident with improvement of HMP shunt metabolism, the Heinz body counts became lower, reduced glutathione higher, hematocrit higher, and liver function improved. Impaired HMP shunt metabolism appears to be a common, acquired RBC abnormality in patients with severe, active liver disease.

Recycling of glucose by rat hepatocytes.

1. The metabolism of glucose labeled uniformly with 14C, and in positions 2, 3 and 5 with tritium by hepatocytes from fed and fasted rats were studied. Cells were incubated with glucose as sole substrate, or with glucose and a variety of glucose precursors, and uptake or production of glucose, and the utilization of the isotopes was determined. 2. There was no uptake of glucose at concentration of up to 15 mM, and net glucose synthesis in the presence of precursors. 14C was however recovered in CO2, lactate and amino acids, and tritium in water. Considerable incorporation into glycogen from 14C and 3H-labeled glucose occurred at high (above 20 mM) glucose concentrations. 3. The yield in water always exceeded that in 14C-labeled products. The yield in 3HOH from [2-3H] glucose exceeded that from [5-3H] glucose, and the latter was greater than from [3-3H] glucose. 4. Utilization of labeled glucose does not follow Michaelis-Menten kinetics. The fractional rate of uptake of 14C and tritium-labeled glucose increases with glucose concentration with a maximum at about 15 mM and then declines. 5. The effect of numerous gluconeogenic substrates on the isotope utilization and the 3H/14C ratio in glycogen was studied. The uptake of 14C was always depressed. Addition of lactate and dihydroxyacetone has little effect on the detritiation of [2-3H] glucose, but it is depressed by other substrates. The detritiation of [3-3H]-and[5-3H]glucose is depressed in gluconeogenesis, that from [3-3H]glucose usually more than from [5-3H]glucose. In the presence of lactate detritiation of [3-3H]glucose is about half that from [5-3H]glucose. 6. Equations to calculate the phosphorylation of glucose and fructose 6-phosphate in the presence of futile cycling between glucose and glucose 6-phosphate and fructose 6-phosphate and fructose 1,6-bisphosphate were derived. 7. The estimate of glucose phosphorylation requires determination of the specific activity of glucose 6-phosphate from [2-3H]glucose. It appears that futile cycling between glucose and glucose 6-phosphate is extensive in cells with a high glycogen content, but is low in cells from starved rats and nearly absent in those from diabetic animals. 8. The estimation of the phosphorylation of fructose 6-phosphate in the presence of cycling requires knowledge of the specific activities of fructose 6-phosphate and fructose 1,6-bisphosphate from [3-3H]glucose. At present there are no adqquate data to calculate phosphorylation and recycling of fructose 6-phosphate, but under some conditions the rate may be quite high.

Glucose Production in the Newborn Dog. I. Effects of Glucagon in Vivo

Extract: Systemic glucose production rates were evaluated 4 hr after feeding in 14 newborn beagle dogs at ages between 1 and 5 days. After a prime injection of radioisotopic tracers, glucose production was determined during infusion of intermixed tracer [2-3H]glucose and [1-14C]glucose at a constant rate. Seven of the newborn dogs served as controls throughout the 3-hr period of infusion, while seven of their littermates, infused simultaneously, received glucagon at a constant rate of 3.3 μg/min between 90 and 180 min of study. In control dogs, mean glucose production, determined by dilution of [2-3H]glucose, was 55 ± 3 μmol/min · kg body weight. During the control period, their littermates produced glucose at a similar rate; however, glucagon infusion raised glucose production to 81 ± 4 μmol/min · kg.The average glucose production rate estimated with [1-14C]glucose was 88% of that with the 3H tracer during the initial control period and 77% during the glucagon infusion. In order to confirm that this discrepancy reflected the recycling of 14C and the early development of gluconeogenesis, an additional 14 newborn dogs were infused with potential substrates for [14C]glucose. In separate studies, [U-14C]lactate, [3-14C]lactate, [U-14C]alanine, and [6-14C]-glucose were incorporated into glucose and [1-14C]glucose. Quantification of gluconeogenesis by simultaneous infusion of [6-3H]glucose and [3-14C]lactate in a 5-day-old dog demonstrated that 25% of the glucose produced originated from lactate, whereas 10% was incorporated into carbon 1. Thus, systemic glucose production was established rapidly in newborn dogs and responded to stimulation with glucagon. A significant proportion of the glucose originated from recycling via the gluconeogenic pathway.Speculation: Even in well nourished newborn mammals, recycling of glucose is important in maintaining homeostasis during the postabsorptive period. Based on comparisons between dogs infused with [3-14C]lactate or [6-14C]glucose, 25% or more of hepatic glucose production may originate from glucose recycled through lactate and pyruvate. Presumably most of the rest is derived from hepatic glycogen stored in utero..

U-14C]glucose metabolism in vivo in rats rendered obese by a high fat diet

Estimates of the glucose pool, the glucose space, the turnover rate, and the recycling of glucose were made after the injection of [U-14C]glucose into (a) obese rats fed a high fat diet and (b) rats fed a carbohydrate diet. The specific activity--time curve consisted of two components. Physiological parameters were calculated by using a two-compartment model. The glucose pool and glucose space were the same in both groups of rats. The turnover rate was 1.96 mg. min-1 for the carbohydrate-fed rats and 1.55 mg. min-1 for the fat-fed rats. There was about 12 percent recycling in both groups. In the carbohydrate-fed group, another approach based on simultaneous use of [6-14C]glucose and [6-3H]glucose yielded nearly the same values for these parameters. Respiratory excretion of CO2 and the incorporation of labeled glucose into lipids of some tissues were also measured. The rate of excretion of labeled CO2 and the conversion of labeled glucose into fatty acids in fat-fed rats were lower than in the carbohydrate-fed rats by 50 percent and 80 percent, respectively. More glucose was diverted into glyceride glycerol in the fat-fed group. It is suggested on the basis of the results that glyceride glycerol can serve as a gluconeogenic substrate in these rats where the turnover rate of glucose is much higher than the daily intake of carbohydrates.

Lactate-glucose interrelations, glucose recycling and the Cori cycle in normal fed rats

1. Turnover and oxidation rates of glucose and lactate were determined using a priming dose-continuous infusion of 14C-(u)-glucose and 14C-(U)-lactate in anesthetized and mechanically ventilated non-fasted rats. The rates of glucose-lactate interconversions were computed from the two-compartment model of Depocas and De Freitas (1970). The rate of total glucose recycling is known as the difference between the rate of true glucose turnover measured with 3H-(2)-glucose (RGT) and the rate of apparent glucose turnover measured with 14C-glucose (RG). This value was compared with the Cori cycle. 2. In normal conditions 17% of RG come from lactate, 43% are directed to lactate and 49% are oxidized. 3. 71% of the rate of lactate turnover come from glucose, 28% are directed to glucose and 51% are oxidized. 4. The rate of total glucose recycling (RGT-RG) is 3.7 mg - mn(-1) per kg0.75 and represents 60% of RG or 38% of RGT. 5. The Cori cycle is 0.8 - 1.2 mg - mn(-1) per kg0.75 and represents 8 - 20% of the rate of glucose turnover and 20 - 32% of total glucose recycling.

Glucose metabolism following severe hemorrhage in the conscious dog.

ARTICLESGlucose metabolism following severe hemorrhage in the conscious dogR Wiener, and JJ SpitzerR Wiener, and JJ SpitzerPublished Online:01 Jul 1974https://doi.org/10.1152/ajplegacy.1974.227.1.63MoreSectionsPDF (960 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByMetabolic Acidosis in the Critically Ill30 May 2008The Diabetogenic Effects of Acute Verapamil PoisoningToxicology and Applied Pharmacology, Vol. 145, No. 2Carbohydrate dynamics in the hypermetabolic septic ratMetabolism, Vol. 33, No. 10The relative prognostic value of lactate and haemodynamic measurements in early shockAnaesthesia, Vol. 39, No. 8The relative prognostic value of lactate and haemodynamic measurements in early shockAnaesthesia, Vol. 39, No. 8Malignant myeloproliferative disorderThe American Journal of Medicine, Vol. 65, No. 2Myocardial oxygen availability and cardiac failure in hemorrhagic shockAmerican Heart Journal, Vol. 92, No. 2Lactate-glucose interrelations, glucose recycling and the Cori cycle in normal fed ratsPfl�gers Archiv European Journal of Physiology, Vol. 361, No. 1 More from this issue > Volume 227Issue 1July 1974Pages 63-66 Copyright & PermissionsCopyright © 1974 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1974.227.1.63PubMed4843356History Published online 1 July 1974 Published in print 1 July 1974 Metrics

Lactate metabolism following severe hemorrhage in the conscious dog.

ARTICLESLactate metabolism following severe hemorrhage in the conscious dogR Wiener, and JJ SpitzerR Wiener, and JJ SpitzerPublished Online:01 Jul 1974https://doi.org/10.1152/ajplegacy.1974.227.1.58MoreSectionsPDF (999 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByQuantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy SourceBioMed Research International, Vol. 2020Retrospective evaluation of the influence of azotemia on plasma lactate concentrations in hypotensive dogs and cats (2008‐2018): 337 cases24 June 2020 | Journal of Veterinary Emergency and Critical Care, Vol. 30, No. 4Quantitative Aspects of L(+)-Lactate Metabolism in Human Beings30 May 2008Metabolic Acidosis in the Critically Ill30 May 2008Mesenteric and Renal Oxygen Transport during Hemorrhage and Reperfusion: Evaluation of Optimal Goals for ResuscitationThe Journal of Trauma: Injury, Infection, and Critical Care, Vol. 51, No. 2Sodium pyruvate is better than sodium chloride as a resuscitation solution in a rodent model of profound hemorrhagic shockResuscitation, Vol. 50, No. 1Transvisceral Lactate Fluxes During Early EndotoxemiaChest, Vol. 110, No. 1Myocardial Metabolism During Graded Intraportal Verapamil Infusion in Awake DogsJournal of Cardiovascular Pharmacology, Vol. 27, No. 5Assessing Perfusion Failure During Circulatory ShockCritical Care Clinics, Vol. 9, No. 2Adult Respiratory Distress Syndrome and Metabolic Organ DysfunctionPercutaneous monitoring of tissue pH with a polymer membrane pH transducerPhase-related changes in tissue energy reserves during hemorrhagic shockJournal of Surgical Research, Vol. 39, No. 5Endocrine Function in the Critically IIIClinics in Anaesthesiology, Vol. 3, No. 4The relative prognostic value of lactate and haemodynamic measurements in early shockAnaesthesia, Vol. 39, No. 8Effect of starvation on the local and systemic metabolic effects of the λ-carrageenan woundThe American Journal of Surgery, Vol. 147, No. 4The relative prognostic value of lactate and haemodynamic measurements in early shockAnaesthesia, Vol. 39, No. 8Is the Use of Isotopic Tracers Valid for the Study of Lactate Metabolism in vivoChanges in the Activities of Enzymes, Especially Lactate Dehydrogenase, in Endotoxin-Poisoned Mice14 November 2013 | Microbiology and Immunology, Vol. 23, No. 7The metabolic utilization of protein and muscle glycogen in experimental shockJournal of Surgical Research, Vol. 26, No. 6Gluconeogenesis from alanine in endotoxin-treated dogsJournal of Surgical Research, Vol. 25, No. 2The effect of a decrease in blood pressure, associated with extracorporeal blood pumping on myocardial metabolism in the isolated dog heart preparationLife Sciences, Vol. 23, No. 1Myocardial oxygen availability and cardiac failure in hemorrhagic shockAmerican Heart Journal, Vol. 92, No. 2Lactate-glucose interrelations, glucose recycling and the Cori cycle in normal fed ratsPfl�gers Archiv European Journal of Physiology, Vol. 361, No. 1 More from this issue > Volume 227Issue 1July 1974Pages 58-62 Copyright & PermissionsCopyright © 1974 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1974.227.1.58PubMed4843355History Published online 1 July 1974 Published in print 1 July 1974 Metrics

Determination of synthesis, recycling and body mass of glucose in rats and rabbits in vivo 3H-and 14C-labelled glucose.

1. Glucose labelled with (3)H in position 2 and uniformly with (14)C was administered simultaneously to rabbits and rats either as a single injection or by continuous infusion. Plasma glucose specific radioactivity and the yield of (3)H in the plasma water were monitored. 2. The rates of synthesis, recycling of carbon and total body mass of glucose were calculated, without assuming a multicompartmental model and without fitting data by exponential expressions. 3. The rate of synthesis of glucose in starved-overnight rabbits was 4mg/min per kg (range 3-4.5mg/min per kg) and 25-35% of the glucose carbon was recycled. The mass of total body glucose in starved rabbits was 290mg/kg (range 220-390mg/kg). About one-third of the total body glucose equilibrates nearly instantaneously with plasma glucose. 4. In rats starved overnight, glucose synthesis was about 10mg/min per kg and recycling of carbon ranged from 30-40%. Total body mass (per kg body weight) is similar to that in rabbits. 5. The activity in plasma water after injection of [2-(3)H]glucose was determined. The initial rate of (3)H(2)O formation is rapid, indicating that the major site of glucose catabolism is in the rapidly mixing pool. The curve of total body glucose radioactivity was obtained from the (3)H(2)O yield, and total mass of glucose was calculated. This agrees with that obtained from the (3)H specific-radioactivity curve.

Utile and futile cycles in the liver

Summary Glucagon or glucose have been administered to normal fed rats in order to induce high rates of glycogen breakdown or synthesis. The administration of glucagon caused a 3-fold increase in the intrahepatic concentration of glucose 6-phosphate. The effect of the administration of glucose on the level of glucose 6-phosphate varied according to whether glycogen synthetase had or not been activated, being slightly elevated in the absence of activation and being lowered (40%) when an important activation had occurred. These observations are discussed with regard to the recycling of glucose and glucose 6-phosphate in the liver. It appears that the advantage of this recycling is to allow large changes in the net flux of metabolites in one or the other direction, controlled by substrate concentration only.

Changes in the Rates of Recycling and Turnover of Glucose during Development of Sheep

The rates of recycling and turnover of glucose in 5-day- and 21-day-old lambs and adult sheep were measured by the method of single simultaneous injection of glucose-6-3H and glucose-6-14C. The 3H/14C ratio decreased linearly with time and was 0.58 and 0.60 in lambs of 5-day- and 21-day-old, respectively, and 0.82 in adult sheep at 120 min after injection of the labeled glucose. The pool size and turnover rate of glucose considerably decreased with age. The rate of glucose recycling was significantly higher in lambs of both ages (22.0 and 26.2%, respectively) than in adult sheep (11.1 %).

Glucose and amino acid metabolism during recovery after exercise.

Glucose and amino acid metabolism during recovery after exercise.

Mechanism of action of biguanides, with special reference to phenethylbiguanide, in the human being

The relationship between inhibition of oxidations by the biguanides and their effect on glucose metabolismin vitro is summarized. Studies on the kinetics of blood glucose in steady state conditions in human subjects treated with phenformin show that the drug increases overall glucose turnover, a significant portion of the increase being due to enhanced recycling of glucose carbon through the Cori cycle. The results of thesein vivo studies are not consistent with thein vitro reports of inhibition of gluconeogenesis. In man the hypoglycemic effect of biguanides could be accounted for by a decrease in glucose absorption by the intestine associated with an increase in peripheral glucose utilization. At the same time, there is an enhancement of gluconeogenesis. The acceleration of glucose removal does not exceed that of glucose synthesis by the liver in non-diabetic subjects in whom the drug does not produce hypoglycemia. The hypoglycemic effect of the drug in diabetic subjects is thought to be a feature of the specific metabolic characteristics of the patient, inducing a limitation of gluconeogenesis, rather than a property of the drug. In the same way, obese diabetics improve their glucose tolerance whereas obese non-diabetics, after prolonged phenformin treatment, become intolerant to glucose. Alcohol infusion after fasting clearly demonstrated that phenethylbiguanide inhibits gluconeogenesis in normal subjects, while in obese, non-diabetics there is a suggestion of gluconeogenesis activation by phenformin. The greatly increased levels of plasma FFA after biguanides, secondary to a decrease in lipogenesis, would further stimulate gluconeogenesis from lactate (derived from glucose utilization in peripheral tissues) which, together with glycerol, arising from adipose tissue lipolysis, could account for the increased glucose synthesis not entirely attributable to glucose recycling through the Cori cycle.

Hypoglycemia associated with extrapancreatic tumors. Report of two cases with studies on its pathogenesis.

Two patients having hypoglycemia associated with extrapancreatic tumors have been described. Patient 1 had poor serum insulin response following the intravenous administration of glucose and tolbutamide and poor growth hormone response to hypoglycemia. The isotopic studies revealed markedly augmented glucose and lactate turnover rates but diminished glucose recycling, indicating inhibited gluconeogenesis. The hypoglycemia was attributed to increased glucose requirements, inhibition of gluconeogenesis, and failure of hormonal homeostasis. The tumor extract revealed nonsuppressible insulin-like activity but no immunoassayable insulin, and failed to produce hypoglycemia in mice in vivo. Patient 2 had adequate serum insulin response following the intravenous administration of glucose. The isotopic studies revealed markedly augmented glucose and lactate turnover rates, as well as increased recycling. The hypoglycemia was attributed to increased glucose requirements. There was no evidence of the inhibition of gluconeogenesis. These studies indicate that hypoglycemia produced by extrapancreatic tumors is multifactorial in etiology and its mechanism varies in different patients.

Glucose-lactate interrelationships: effect of ethanol.

The effect of ethanol on the interrelationship of lactate and glucose metabolism was investigated in eight human volunteers. Lactate and glucose kinetics and intervconversion rates were determined by the sequential administration of L-(+) lactate-U-(14)C and glucose-1-(14)C over an 8 hr period. After a 12 hr fast, the glucose turnover and recycling rates were 94.0 +/-3.8 (SEM) and 13.7 +/-1.1 mg/kg per hr, respectively. Approximately 50% of the glucose turnover or 40.7 +/-2.1 mg/kg per hr was converted to lactate, accounting for 50% of the lactate turnover rate. Lactate turnover and lactate conversion to glucose were 81.8 +/-6.2 and 16.7 +/-1.1 mg/kg per hr, respectively. Approximately 20% of the glucose turnover was derived from lactate under these conditions. During the administration of ethanol, the blood lactate concentration doubled and the lactate turnover rate declined slightly. Lactate conversion to glucose was markedly inhibited, decreasing from 16 to 5 mg/kg per hr, and the per cent of the glucose turnover derived from lactate decreased from 18 to 6. Despite the marked inhibition of lactate conversion to glucose, neither the blood glucose concentration nor the glucose turnover rate changed. Both glucose recycling and glucose conversion to lactate were decreased, indicating that ethanol inhibited peripheral glucose utilization. There was no difference in the degree of inhibition of lactate incorporation into glucose produced by ethanol when nonfasted subjects were compared with two subjects who had fasted for 48-72 hr despite the presence of hypoglycemia in the latter. These results indicate that starvation is not a prerequisite for ethanol inhibition of gluconeogenesis from lactate in humans but is necessary for the development of hypoglycemia. Inhibition of lactate incorporation into glucose in nonfasted subjects is probably masked by a concomitant increase in glycogenolysis which prevents hypoglycemia. Ethanol decreases glucose conversion to lactate as well as lactate conversion to glucose, thus inhibiting the Cori cycle.

Lactate turnover and gluconeogenesis in obesity. Effect of phenformin.

The effect of phenformin on the rates of lactate and glucose turnover, interconversion, and oxidation was determined in five obese subjects with normal glucose tolerance. L (+) lactate-U (50 μc.) and glucose 1-C-14 were administered over four-hour periods on consecutive days by a primed infusion technic. One hundred to 150 mg. of phenformin was administered daily, and the turnover studies were repeated on the sixth and seventh days of therapy. Phenformin increased glucose turnover by 10 per cent, from 95.6 ± 4.4 to 106.2 ± 4.7 (mean ± S.E.M.) mg,/kg./ hr. and glucose recycling by 100 per cent, from 8.7 ± 1,4 to 19.3 ± 1.3 mg./kg./hr. In contrast, the changes in glucose oxidation were inconsistent, decreasing in three subjects and increasing in two. As expected, the blood glucose concentration and glucose pool were unchanged during treatment with phenformin. Lactate turnover increased 30 per cent, from 63.5 ± 3.5 to 82.8 ± 5.7 mg./kg./hr., and lactate derived from glucose (glucose conversion to lactate) increased 25 per cent, from 57.9 ± 5.5 to 71.8 ± 6.9 mg./kg./hr. Lactate conversion to glucose increased in all subjects by a mean of 13.1 ± 1.2 mg./kg./hr., from 15.2 ± 1.2 to 28.2 ± 1.8 mg./kg./hr. The increase in lactate conversion to glucose was almost identical to the increase in glucose turnover and glucose conversion to lactate. During therapy with phenformin, 34.1 ±1.2 per cent of the lactate turnover was converted to glucose in contrast to 22.1 ± 1.3 per cent before therapy. These results demonstrate that phenformin enhances the interconversion of glucose and lactate in subjects in whom it exerts no hypoglycemie effect.

Effect of Phenformin in nondiabetic humans. Estimation of glucose turnover rate and Cori Cycle activity

Glucose turnover and the rate of recycling of glucose carbon into glucose, before and after a two day course of Phenformin 100 mg./day, has been evaluated with the aide of C-6 labeled 14C glucose in the nondiabetic human subject. These studies providing a measure of true glucose turnover and utilizing each subject as his own control support earlier data on this aspect of the action of Phenformin that had been obtained with uniformly labeled glucose in two groups of nondiabetic subjects. Direct evidence of increased Cori Cycle activity as measured by the appearance of 14C label in the C-(1–5) moiety of glucose and the evidence that glucose turnover increased by a factor of 2x the increase in the rate of glucose recycling suggest that gluconeogenesis is stimulated when this drug is given to humans. Ancillary measurement of the rate of glucose oxidation before and after Phenformin shows a slight stimulation of this aspect of glucose metabolism in the nondiabetic human following the drug, a finding that is concert with an earlier demonstration of significant increases in glucose oxidation in diabetic subjects treated with Phenformin.

Glucose metabolism in normal and obese subjects. Effect of phenformin.

The purpose of the experiments described in this paper was to determine whether phenformin altered the metabolism of glucose in subjects in whom it did not lower the blood sugar. Glucose-1-C-14 was utilized to investigate the metabolism of glucose in eight normal and eight obese subjects before and after phenformin. Phenformin increased the turnover, recycling and conversion of glucose to lactate and decreased the oxidation of glucose in all of the normal subjects studied. The increase in glucose turnover was due entirely to the increase in glucose recycling since net glucose turnover (glucose derived from all sources except the Cori cycle) did not change. Phenformin also increased glucose turnover and recycling in obese subjects but in contrast to normals, its effect.s on glucose oxidation and glucose conversion to lactate were more variable. These results establish that phenformin has clearly defined effects on the metabolism of glucose in subjects in whom it exerts no hypoglycemic action and support the concept that phenformin increases glucose utilization by diverting it from oxidative to nonoxidative pathways in peripheral tissues.

Rate of glucose transformation in the rat by whole-body analysis after blucose-14-C.

Rate of glucose transformation in the rat by whole-body analysis after blucose-14-C.

Glucose metabolism and plasma insulin level during epinephrine infusion in the dog.

Glucose metabolism and plasma insulin level during epinephrine infusion in the dog.