Glucose utilization and recycling in ponies.

Variables of glucose metabolism determined by the use of [U-14C]glucose were compared in fed and fasted ponies. Relative recycling of glucose carbon with respect to tritium in fed animals was negligible for 6-T and 3-T and 16% for 2-T studies; in fasted animals relative recycling was 12 and 14% for 6-T and 3-T studies, respectively. Minimal mass of total-body glucose decreased significantly in the fasted ponies. Based on relative recycling of carbon to tritium, a negligible fraction of plasma glucose was produced via the Cori cycle or from glycerol in fed ponies; recycled tricarbon units contributed 12% of glucose produciton in ponies fasted 72 h. In fed ponies, 16% of plasma glucose carbon was recycled via a futile cycle at the glucose 6-phosphate stage. Glucose utilization was best estimated with the use of [6-T]glucose (or 3-T).     

Glucose turnover values in the dog obtained with various species of labeled glucose.

Recent studies proposed that [2T]glucose is preferable to [14C]-glucose as a tracer for the measurement of glucose turnover. However, higher values for glucose turnover were obtained using [2T]glucose than with [14C]glucose. The present study explores the merit of another species of tritiated glucose, [3T]glucose. Utilizing isotope-dilution principles, comparison is made of glucose turnover values determined by use of [2T]glucose, [3T]glucose, and [6-14C]glucose. Glucose turnover using [2T]glucose was 1.51 +/- 0.07 times greater than that using [6-14C]glucose, after correction for recycling of 14C. However, glucose turnover values obtained with [3T]glucose were similar to those obtained with [6-14C]glucose. There were no temporal or quantitative differences in appearance of tritium (T) in plasma water after injection of [2T]- and [3T]glucose. A methylprednisolone regimen in the normal dog increased glucose turnover as determined by all three tracers, but the increase observed using [2T]glusoce was significantly greater than that using that two other tracers. Thiement for [6-14C]glucose for measurement of glucose turnover in the dog.     

Fructose-6-phosphate substrate cycling and glucose and insulin regulation of gluconeogenesis in vivo.

The question whether glucose or insulin regulates gluconeogenesis by effecting changes in the fructose-6-phosphate (F-6-P) substrate cycle (phosphofructokinase (PFK), fructose-1,6-diphosphatase (FDPase)) was investigated in vivo in fasted normal rats using [3-3H,U-14C]- or [3-3H,6-14C]glucose. The plasma glucose 3H/14C ratio was used as an index of substrate cycling because 3H loss from the liver hexose phosphate pool is limited by the activities of PFK and FDPase during gluconeogenesis and glycolysis, respectively. The 3H/14C ratio was corrected where necessary for glucose or insulin-induced changes in reincorporation of 14C from C-6 to C-1-3 of plasma glucose. A glucose infusion producing hyperglycemia and insulinemia was accompanied by decreased hepatic glucose production and diminished F-6-P substrate cycling, i.e., decreased FDPase activity. When insulin was infused along with glucose to produce high plasma insulin levels and avoid hypo- or hyperglycemia, the 3H/14C decay rate did not change, suggesting that the hormone does not influence basal rates of gluconeogenesis or PFK or FDPase activities. These in vivo results suggest that increased blood glucose levels inhibit gluconeogenesis and depress F-6-P substrate cycling. Whether these cycle changes constitute primary regulatory actions of glucose or occur secondarily to other metabolic events resulting from excess hexose (e.g., increased glycogen synthetase activity) cannot now be concluded.     

Kinetics of lactate and glucose metabolism in the pregnant ewe and conceptus

Two monotocous and two ditocous ewes were infused at 124-130 days of gestation with a mixture of L-[U-14C]lactate and D-[6-3H]glucose via a maternal or umbilical catheter, separate days being used for each infusion. Plateaux-specific radioactivities of plasma lactate and glucose were used to derive a four-pool model describing the fluxes between the lactate and glucose pools of the infused conceptus and mother. The average turnover rate of lactate was 23.3 and 13.2 mg carbon min-1 in the conceptus and 32.0 and 44.0 mg carbon min-1 in the mother for monotocous and ditocous ewes, respectively. Glycolysis rates within both conceptus and mother in all sheep were high, accounting for about 80 and 60% of the respective rates of lactate turnover. The synthesis of glucose from lactate accounted for 13 and 31% of the glucose turnover in the mother in monotocous and ditocous ewes, respectively, but was insignificant in the conceptus. Glycolysis within the conceptus used only glucose which had entered and mixed with the conceptus glucose pool; there was no direct transfer of carbon from the maternal glucose pool to the conceptus lactate pool. This finding is an important validation for the use of tracer methods to determine glucose use within the whole conceptus rather than within fetal corporeal tissues alone.     

Integration of [U-13C]glucose and 2H2O for quantification of hepatic glucose production and gluconeogenesis

Glucose metabolism in five healthy subjects fasted for 16 h was measured with a combination of [U-13C]glucose and 2H2O tracers. Phenylbutyric acid was also provided to sample hepatic glutamine for the presence of 13C-isotopomers derived from the incorporation of [U-13C]glucose products into the hepatic Krebs cycle. Glucose production (GP) was quantified by 13C NMR analysis of the monoacetone derivative of plasma glucose following a primed infusion of [U-13C]glucose and provided reasonable estimates (1.90 +/- 0.19 mg/kg/min with a range of 1.60-2.15 mg/kg/min). The same derivative yielded measurements of plasma glucose 2H-enrichment from 2H2O by 2H NMR from which the contribution of glycogenolytic and gluconeogenic fluxes to GP was obtained (0.87 +/- 0.14 and 1.03 +/- 0.10 mg/kg/min, respectively). Hepatic glutamine 13C-isotopomers representing multiply-enriched oxaloacetate and [U-13C]acetyl-CoA were identified as multiplets in the 13C NMR signals of the glutamine moiety of urinary phenylacetylglutamine, demonstrating entry of the [U-13C]glucose tracer into both oxidative and anaplerotic pathways of the hepatic Krebs cycle. These isotopomers contributed 0.1-0.2% excess enrichment to carbons 2 and 3 and approximately 0.05% to carbon 4 of glutamine.     

Altered metabolic priming by D-glucose in pancreatic islets from Goto-Kakizaki rats

The possible priming by D-glucose of metabolic events in islets from control rats and Goto-Kakizaki rats (GK rats) was investigated by first incubating the islets for 120 min either in the absence of any exogenous nutrient or presence of 16.7 mM D-glucose. The islets were then incubated for a second period of 120 min either at 2.8 mM or 16. 7 mM D-glucose, the hexose being now mixed with tracer amounts of D-[U-14C]glucose and D-[5-3H]glucose. In islets from control rats first incubated in the absence of exogenous nutrient the hierarchy in the 16.7 mM/2.8 mM ratio for metabolic variables was as follows: D-[U-14C]glucose oxidation > D-[5-3H]glucose utilization and D-[U-14C]glucose conversion to amino acids > D-[U-14C]glucose conversion to acidic metabolites. When the islets from control rats were first incubated in the presence of 16.7 mM D-glucose, the preferential stimulation of mitochondrial oxidative events at high hexose concentration, as documented by the increase in the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization, was further enhanced. The 16.7 mM/2.8 mM ratio for the conversion of D-[U-14C]glucose to amino acids, relative to that for D-[U-14C]glucose conversion to acidic metabolites, was much lower, however, after a first incubation in the presence of D-glucose, rather than in its absence, probably as a result of the progressive exhaustion of endogenous amino acids considered as transamination partners. The major differences between these results and those obtained in islets from GK rats consisted, in the latter animals, in i) higher absolute values for all metabolic fluxes, ii) lower 16.7 mM/ 2.8 mM ratios, iii) lower paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization, and iv) absence of a priming effect of D-glucose (16.7 mM) upon such a paired ratio in the islets incubated at 16.7 mM D-glucose during the second incubation. Taken as a whole, these observations confirm that the preferential stimulation of mitochondrial oxidative events, in response to a rise in D-glucose concentration, is impaired in islets from GK rats and extend this knowledge to the priming action of D-glucose, in high concentration, on the catabolism of the hexose during a subsequent incubation.     

Metabolism of D-[3-3H]glucose, D-[5-3H]glucose, D-[U-14C]glucose, D-[1-14C]glucose and D-[6-14C]glucose in pancreatic islets in an animal model of type-2 diabetes

This study aims at exploring specific aspects of D-glucose metabolism, so far not yet investigated, in pancreatic islets from adult control rats and animals (STZ rats) injected with streptozotocin during the neonatal period. The latter animals, which represent a current model of type-2 diabetes, displayed a lower body weight, higher plasma D-glucose concentration and lower insulinogenic index than control rats. The protein, DNA and insulin content were all also lower in islets prepared from STZ, rather than control rats. In the presence of 10.0 mM D-glucose, the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was also decreased in the islets from STZ rats. No significant difference between control and STZ rats was observed, however, in terms of the ratios between D-[3-3H]glucose and D-[5-3H]glucose utilization, between the generation of radioactive lactate from 14C-labelled D-glucose and tritiated D-glucose utilization and between D-[1-14C]glucose and D-[6-14C]glucose oxidation. These findings reinforce the view that the previously documented preferential impairment of the oxidative modality of glycolysis in islets from STZ rats contrasts with the absence of any major anomaly in other variables of D-glucose catabolism.     

Effect of perfusate glucose concentration on rat lung glycolysis.

We investigated the relationship between perfusate concentration of glucose and its utilization and lactate production derived from exogenous glucose and from metabolism of endogenous substrates. Isolated rat lungs were ventilated with 5% CO2 in air and perfused for 100 min with Krebs-Ringer bicarbonate buffer containing 3% bovine serum albumin, 10(-2) U/ml insulin, [U-14C]glucose and [5-3H]glucose. Glucose utilization, total lactate production, [14C]lactate production, and 3H2O production were measured. The apparent Km and Vmax for glucose utilization were 3.4 mM and 72.5 mumol/g dry wt per h, respectively. Lactate production from endogenous substrates, calculated as the difference between total and [14C]lactate, was 37.6 +/- 2.2 mumol/g dry wt (n = 36); it was unaffected by perfusate glucose concentration and by omission of insulin, but increased threefold with anoxia. Lactate production from 1.5 mM glucose was significantly less (P less than 0.02) with insulin omitted. Glycogen content was unchanged during perfusion without glucose. These results suggest that: 1) protein catabolism contributes to lung lactate production; 2) glucose utilization by lung is not maximal at resting physiological glucose concentrations; and 3) insulin is required at low glucose concentrations for maximal glycolytic rates.     

Ouabain-sensitive carrier-mediated transport of glucose from the cerebral ventricles to surrounding tissues in the cat

1. Artificial cerebrospinal fluid containing isotopically labelled sugars was perfused from the lateral cerebral ventricles to an effluent catheter inserted into the cerebral aqueduct of anaesthetized cats. This system was used for a quantitative study of the absorption of the sugars during steady state.2. A saturable mechanism was involved in the absorption of [U-(14)C]D-glucose and [(14)C]D-galactose. Absorption of [U-(14)C]D-glucose in the dead animal was similar to that of [(3)H]D-mannitol.3. 5 x 10(-5)M ouabain in the inflow reduced cerebrospinal fluid formation and the unidirectional fluxes of glucose from the ventricles into brain tissue and plasma. Ouabain did not alter the absorption of [(3)H]D-mannitol.4. Three types of unidirectional fluxes of glucose from the cerebral ventricles were separated. One was ouabain-sensitive and followed Michaelis-Menten kinetics. The second was insensitive to ouabain and the third occurred by simple diffusion.5. At normal ventricular glucose concentrations (3.5 mM) the three fluxes comprised (roughly): 25% (ouabain-sensitive), 35% (ouabain-insensitive) and 40% (simple diffusion) of total, unidirectional transport.     

Effects of selective insulin or glucagon deficiency on glucose turnover.

To study the importance of glucagon and insulin in diabetes, somatostatin (ST) was infused, alone or with insulin or glucagon, in 11 conscious dogs. Plasma immunoreactive insulin (IRI) and glucagon (IRG) levels fell 65 +/- 4% and 33 +/- 3%, respectively, with somatostatin infusion. Glucose production (Ra) assessed by [3-3H]glucose, [2-3H]glucose, or [1-14C]glucose decreased transiently. This is in contrast to the rise in Ra seen after insulin withdrawal in depancreatized dogs, which have normal levels of IRG. Thus, suppression of IRG with somatostatin prevented an increase in Ra in spite of suppression of IRI. When near basal IRG levels were provided during ST infusion in normal dogs, Ra increased, indicating that glucagon contributes to the acute development of diabetes. When basal IRI levels were provided with ST, suppression of Ra was maintained, suggesting that the transience of the metabolic effects of ST-induced glucagon suppression requires concomitant insulin suppression. A comparison of glucose turnover measured using different tracers showed that ST-related hormonal changes did not alter the rate of futile cycling in the liver. ST induced a rise in plasma free fatty acid (FFA) levels, attributed solely to insulin deficiency, as glucagon suppression did not significantly alter FFA concentrations when normal insulin levels were maintained.     

U-14C]glucose, -alanine, and -leucine oxidation in rats at rest and two intensities of running

The oxidations of injected [U-14C]glucose, [U-14C]alanine, and [U-14C]leucine were investigated in laboratory rats during rest or 2 h of easy and hard treadmill running. After [U-14C]glucose injection, the rate and magnitude of 14CO2 evolution were relatively low at rest and increased as a linear function of metabolic rate (VO2). Evolution of 14CO2 after [U-14C]alanine injection was faster and larger during exercise than rest. The peak of alanine decarboxylation occurred before glucose and, therefore, did not reflect conversion of alanine to glucose prior to decarboxylation. The rate and magnitude of 14CO2 evolution after [U-14C]leucine injection were proportional to metabolic rate, but less than after glucose or alanine injection. During exercise, levels of alanine and leucine in muscle and blood were unchanged or elevated compared to rest. During exercise, alanine levels were unchanged or increased in liver. Liver leucine levels were depressed when exercise began, but increased toward control values during exercise. The metabolism of selected amino acids is joined to carbon flow sustaining exercise.     

Effects of gliquidone on D-glucose metabolism in rat pancreatic islets depend on hexose concentration

The hypoglycemic sulfonylurea gliquidone, used at a 10 microM concentration, failed to affect the metabolism of D-glucose in rat pancreatic islets incubated in the presence of 5.6 mM, 8.3 mM or 16.7 mM D-glucose. However, at 2.8 mM D-glucose, gliquidone increased D-[U-14C]glucose oxidation while decreasing the utilization of D-[5-3H]glucose and generation of radioactive acidic metabolites and amino acids from D-[U-14C]glucose. These dissociated effects could conceivably be attributable, respectively, to activation of FAD-linked glycerophosphate dehydrogenase as a result of an increase in cytosolic Ca2+ concentration and to a subsequent inhibition of phosphofructokinase as a result of an increase in cytosolic ATP concentration. The effect of gliquidone on the paired ratio between D-[U-14C]glucose oxidation and D-[5-3H]glucose utilization was indeed duplicated by repaglinide and suppressed in the absence of extracellular Ca2+ or at low temperature. The present findings thus provide a further illustration of the often contrasting effects of pharmacological and physiological insulinotropic agents on selected metabolic, cationic and functional variables in pancreatic islet cells.     

Alterations of glucose metabolism during perfusion of rat lung with paraquat.

Isolated perfused rat lungs were used to investigate effects of paraquat on lung glucose metabolism. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate buffer, pH 7.4, containing albumin and 5.5 mM radiolabeled D-glucose. Control lung glucose utilization, estimated from rate of 3H2O production from [5-3H]glucose, was 44 mumol/h-g dry wt. Pentose cycle activity, based on 14CO2 specific yields at the end of perfusions with [1-14C]- and [6-14C]glucose, was 14% of glucose utilization. During perfusion with 1.5 mM paraquat, glucose utilization increased 28%, 14CO2 production via the pentose cycle increased 182% (P less than 0.005), CO2 production via mitochondrial metabolism increased 39% (P less than 0.02), and the rate of lactate production increased 28% (P less than 0.05). Pyruvate production and the lactate-to-pyruvate ratio were not significantly altered. The data indicate that interaction of paraquat with the lung results in increased turnover of cytoplasmic NADPH and increased mitochondrial metabolism, but no significant change in cytoplasmic redox state. The findings are compatible with intracellular enzymatic reduction of paraquat by an NADPH-requiring reductase.     

The oxidation of glucose, ketone bodies and acetate by the brain of normal and ketonaemic sheep.

1. The utilization and oxidation of glucose, acetate and ketone bodies by the brain of sheep has been determined from measurements of arteriovenous (A-V) differences and cerebral blood flow, as well as by infusing 14C-labelled metabolites. 2. The A-V difference for glucose was generally more than one sixth, on a molar basis, that of oxygen. 3. The mean rate of glucose utilization by the brain of conscious sheep (0-508 +/- 0-063 mumole/g per minute) was maintained even when the capillary glucose concentration was below 1-4 mM. 4. The amount of 14CO2 produced from [U-14C]glucose by the brain was consistent with glucose being the only energy source for the brain, even during hypoglycaemia and hyperketonaemia. 5. There was no appreciable production of lactate or pyruvate by the brain. 6. There was no significant A-V difference for acetate across the brain in normal or undernourished pregnant sheep. The small A-V differences that were measured show that less than 5% of the CO2 produced could be derived from acetate, a conclusion that is supported by experiments using [U-14C]acetate. 7. No significant A-V difference was detectable across the brain for 3-hydroxybutyrate or acetoacetate in normal fed, pregnant ketonaemic or even anaesthetized sheep infused with acetoacetate. Experiments in which [U-14C]-D(-)-3-hydroxybutyrate was infused also showed that less than 5% of CO2 was derived from ketone bodies. 8. In anaesthetized sheep infused with acetoacetate, measurements were made simultaneously across brain, heart and skeletal muscle. In contrast to the non-significant uptake of ketone bodies by the brain, uptake by heart and skeletal muscle was sufficient to account for nearly 60% of their oxygen consumption. 9. Experiments using [14C]hydroxybutyrate confirmed that during infusion of acetoacetate most of the CO2 produced by the heart, but not by the brain, was derived from ketone bodies. 10. In anaesthetized sheep ketone bodies penetrate only slowly into cerebrospinal fluid. 11. It is proposed that mechanisms for the utilization of ketones by the sheep brain have not evolved because glucose utilization by the brain is a smaller fraction of whole body glucose utilization than in man and rats.     

The effect of insulin and insulin deficiency on the transport and metabolism of glucose by rat small intestine

1. Insulin deficiency induced by anti-insulin serum or streptozotocin increased glucose absorption, as measured in everted sacs of rat upper ileum incubated for 30 min with oxygenated Krebs-Henseleit bicarbonate medium.2. Everted sacs prepared from the terminal ileum of insulin-deficient rats were able to accumulate glucose against a concentration gradient (i.e. development of active glucose transport).3. In experimental diabetes induced by streptozotocin, everted sacs of upper ileum showed increased 3-methyl glucose active transport, and sacs of terminal ileum showed development of 3-methyl glucose active transport.4. Lactic acid formation during the absorption of both glucose and 3-methyl glucose was increased approximately twofold in everted sacs of insulin-deficient animals.5. Insulin added at 100 mu./ml. to the incubating media of everted sacs prepared from insulin-deficient rats did not result in a reduction of glucose absorption or reverse the other effects.6. Fluoride (5 x 10(-3)M) added to the serosal and mucosal media of sacs of terminal ileum prepared from insulin-deficient rats decreased [(14)C]CO(2) formation from [U-(14)C]glucose and lactate formation during glucose absorption, but was unable to reverse the effect of insulin deficiency on glucose active transport.7. The effects of insulin deficiency induced by streptozotocin were more striking than those induced by anti-insulin serum.8. Everted sacs prepared from rats starved for 3 days showed increased glucose active transport accompanied by diminished conversion of [U-(14)C]glucose to [(14)C]CO(2).9. The possible role of hexokinase is discussed in relation to these findings.     

Metabolic response to carbon monoxide by isolated rat lungs.

Glucose metabolism was studied in isolated rat lungs ventilated with 95% O2.5% CO2 (control), 95% N2: 5% CO2 (hypoxia), and 95% CO:5% CO2 (carbon monoxide) and perfused for 100-120 min with Krebs-Ringer-bicarbonate buffer, pH 7.4, containing [U-14C] and [3-3H]glucose. The production of 14C-labeled lactate plus pyruvate (L + P) and of 14CO2 represented 48% and 22% respectively, of the total [14C]glucose utilization. The lactate-to-pyruvate ratio (L/P) was 8.7. Tritium was recovered predominantly as 3H2O in the perfusate. Wth carbon monoxide ventilation, L + P production was increased by 357% with an L/P of 52.9, and 14CO2 production was markedly decreased. A 56% decrease in lung ATP content was associated with decreased incorporation of 14C into fatty acids. Compared with CO, changes with N2 ventilation were less marked, indicating that ventilation with CO is a more effective method with which to study inhibtion of oxidative metabolism. The lung exhibits a Pasteur effectbintain ATP content or its supply for synthetic activity.     

Substrate cycling between glucose 6-phosphate and glycogen occurs in Schistosoma mansoni

The regulation of glycogen metabolism in Schistosoma mansoni was studied in vitro with special emphasis on the possible occurrence of substrate ('futile') cycling. The partition of label between carbon atoms 1 and 6 of the glucose units in glycogen was analysed after the incubation of intact worm pairs in the presence of [6-14C]glucose. Under all conditions tested, more than 99% of the label in glycogen was still in the 6 position, demonstrating that glycogen was synthesised not via an indirect pathway involving 3-carbon units, but directly, from glucose. Increasing the glucose concentration stimulated glycogen synthase and decreased the activity of glycogen phosphorylase. An inverse relationship was shown between the actual glycogen content and the rate of glycogenesis. Substrate cycling occurred between glucose 6-phosphate and glycogen. Glucose was incorporated into glycogen during periods of net glycogen breakdown, and vice versa: glycogen degradation occurred during periods of net glycogen synthesis. Under our experimental conditions of net glycogen degradation, the rate of glycogen synthesis as a percentage of that of glycogen breakdown was dependent on the external glucose concentration and ranged from 5 to 68% for 2 to 100 mM glucose, respectively. The synthesis of glycogen during periods of net glycogen breakdown was shown to occur in each individual worm pair.     

Steady-state glucose oxidation by dog kidney in vivo: relation to Na+ reabsorption.

In eight experiments at normal or slightly elevated blood glucose concentration we quantified the steady-state renal glucose oxidation rate (see article) during control, at reduced Naomega absorptive rates (raised ureteral pressure), and during respiratory alkalosis. A tracer amount of either [1-14C]glucose or or [U-14C]D(omega)-glucose was infused at a constant rate into one renal artery. (see article) was calculated from the renal 14CO2 production rate (corrected for recirculation) and the specific activity of glucose in renal arterial blood. The control (see article) (n equals 8) equals 4.40 plus or minus 0.9 mumol/100 g-min (mean plus or minus SE). When net Naomega reabsorption was decreased by 45% (n equals 6), or when the pH of extracellular fluid was raised (n equals 2), no significant effect on (see article) (9.1 plus or minus 4.2 and 3.9 plus or minus 2.3 mumol/min-100 g, respectively) occurred. The mean glucose oxidation rate for all experiments was 5.65 plus or minus 1.73 mumol g-1-min-1 and required similar to 13% of the renal O2 utilization. Glucose oxidation provides energy either for basal renal work or for some portion of renal transport work not affected by increased ureteral pressure.     

Effect of fasting and refeeding on glucose metabolism in rat aorta

The effect of refeeding on accumulation of [14C]glucose carbon, oxidation of [14C]glucose and glycogen concentration in rat aortic intima-media was studied in rats fasted for 3 days. Accumulation of glucose carbon and glucose oxidation were determined by incubating rat aorta in vitro for 2 h with 5.6 mM 14C-labelled glucose in the medium. Refeeding with standard pellets for 2-4 h augmented [14C]glucose accumulation in rat aorta but had no significant effect on glucose oxidation. The glycogen concentration in rat aorta tended to increase. After refeeding for 16 h both [14C]glucose incorporation and [14C]glucose oxidation were increased in rat aorta. Refeeding with carbohydrate-rich pellets (92% carbohydrate) for 3 h increased blood glucose more than did protein-rich (92% protein) pellets, whereas the rise in plasma insulin was about the same. The accumulation of [14C]glucose carbon measured during the subsequent in vitro incubation for 2 h was augmented after refeeding with protein-rich pellets and slightly reduced after carbohydrate-rich pellets. Refeeding of diabetic rats for 2 h with standard pellets increased plasma insulin and markedly increased blood glucose but had no effect on aortic [14C]glucose incorporation. Intravenous infusion of glucose in normal rats for 2 h markedly raised blood glucose but did not increase the aortic glucose incorporation. Raising the ambient glucose concentration from 5 to 10 mM during incubation of normal rat aorta in vitro for 2 h slightly decreased the [14C]glucose incorporation determined during a subsequent incubation for 2 h. These results suggest that refeeding with standard pellets augments glucose incorporation and glucose oxidation in rat aorta.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of in vivo exposure to insulin on glucose metabolism in rat aorta

The effect of administration of insulin in vivo on accumulation of [14C]glucose carbon in rat aorta in vitro was studied. Insulin was injected intravenously in a tail vein 5-60 min before the rats were killed and the accumulation of [14C]glucose was determined after incubation for 30-120 min in 5.6 mM [14C]glucose. When determined 30 min after injection of insulin (4 U kg-1) the aortic [14C]glucose incorporation was significantly increased when an incubation period of 120 min was used, while no significant effect was found after incubation for 30 or 60 min. In subsequent experiments an incubation time of 120 min was used. The aortic [14C]glucose accumulation was not increased when determined 5 or 60 min after injection of insulin (4 U kg-1). Injection of insulin (2 U kg-1) 5 or 30 min before the rats were killed had no effect on the aortic [14C]glucose accumulation but it had a pronounced effect on [14C]glucose accumulation in rat diaphragm. Serum insulin determined 30 min after injection of insulin (2 U kg-1) was 731 +/- 58 mU-1 and in saline-treated control rats 37 +/- 3 mU l-1. These results suggest that the glucose metabolism of vascular smooth muscle has a low sensitivity to the immediate effects of insulin.