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At least 19 recordsLinked to original sources
PubMed2002

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.

Animals↗
PubMed1995

Metabolism of D-[1-3H]glucose, D-[2-3H]glucose, D-[5-3H]glucose, D-[6-3H]glucose and D-[U-14C]glucose by rat and human erythrocytes incubated in the presence of H2O or D2O.

The present study investigates whether heavy water affects the efficiency of 3HOH production from D-[1-3H]glucose, D-[2-3H]glucose, D-[5-3H]glucose and D-[6-3H]glucose relative to the total generation of tritiated metabolites produced by either rat or human erythrocytes. The relative 3HOH yield was close to 95% with D-[5-3H]glucose, 72% with D-[2-3H]glucose, 22-32% with D-[1-3H]glucose, and only 12% with D-[6-3H]glucose. In the latter case, the comparison of the specific radioactivity of intracellular and extracellular acidic metabolites, expressed relative to that of 14C-labelled metabolites produced from D-[U-14C]glucose, indicated that the generation of 3HOH from D-[6-3H]glucose occurs at distal metabolic steps, such as the partial reversion of the pyruvate kinase reaction or the interconversion of pyruvate and L-alanine in the reaction catalysed by glutamate-pyruvate transaminase. As a rule, the substitution of H2O by D2O only caused minor to negligible changes in the relative 3HOH yield. This implies that the unexpectedly high deuteration of 13C-labelled D-glucose metabolites recently documented in erythrocytes exposed to D2O cannot be attributed to any major interference of heavy water with factors regulating both the deuteration and detritiation efficiency, such as the enzyme-to-enzyme tunnelling of specific glycolytic intermediates.

Animals↗
PubMed1992

Use of [3-3H]glucose and [6-14C]glucose to measure glucose turnover and glucose metabolism in humans.

[3-3H]glucose is frequently used to measure glucose turnover in humans. If fructose 6-phosphate-fructose 1,6-diphosphate cycling (Fpc) is negligible in both liver and muscle, then [3-3H]- and [6-14C]glucose (corrected for Cori cycle activity) should provide equivalent measures of glucose turnover. In addition, if glycogenolysis is fully suppressed, then [14C]lactate specific activity should equal that of [6-14C]glucose from which it was derived, and oxidation of [6-14C]glucose, as measured by rate of generation of 14CO2, should equal total glucose oxidation (i.e., that derived from intra- and extracellular pools) as measured by indirect calorimetry. To address these questions, glucose turnover was measured simultaneously with [3-3H]- and [6-14C]glucose in the basal state and in presence of low (approximately 200 pM) and high (approximately 750 pM) insulin concentrations. Glucose turnover rates measured with [3-3H]- and [6-14C]glucose were equivalent at all insulin concentrations, indicating that Fpc had no detectable effect on measurement of glucose appearance. [14C]lactate specific activity was lower (P less than 0.01) than that of [6-14C]glucose in the basal state but not during either low- or high-dose insulin infusion, implying that all lactate was derived from extracellular glucose. On the other hand, glucose oxidation as measured by rate of generation of 14CO2 was lower (P less than 0.05) than glucose oxidation as measured by indirect calorimetry during both insulin infusions, implying either that suppression of glycogenolysis was not complete in all tissues or that one or both of these techniques do not accurately measure glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Values of fasting glucose levels, glucose tolerance tests, and glucose-insulin ratios as predictors of glucose tolerance.

OBJECTIVE: To examine the ability to use parameters obtainable from an oral glucose tolerance test to predict insulin action as determined under hyperinsulinemic, hyperglycemic conditions. DESIGN: Prospective clinical investigation. SETTING: University medical center clinical research unit. PATIENT(S): Healthy male volunteers. INTERVENTION(S): Oral glucose tolerance test and hyperglycemic (+125 mg/dL) clamp studies. MAIN OUTCOME MEASURE(S): Glucose and insulin (I) levels, rate of glucose uptake (M) under hyperglycemic conditions, and M/I ratios. RESULT(S): Among individuals with normal glucose tolerance, as assessed by an oral glucose tolerance test, the fasting insulin level is the glucose tolerance test parameter that correlates best with insulin action during a hyperglycemic clamp. CONCLUSION(S): Measurement of fasting serum insulin levels in conjunction with an oral glucose tolerance test improves the ability to assess insulin action. Such combinations may improve the ability to diagnose insulin-resistant states.

Adult↗
PubMed1980

Glucose disappearance in infants of diabetic mothers. III. Relationship of spontaneous glucose disappearance to glucose tolerance, neonatal hypoglycemia and lowest blood glucose.

Spontaneous glucose disappearance in the first 90 min of life and glucose disappearance following an intravenous injection of 1 g/kg dextrose were measured in 23 infants of insulin-dependent diabetic mothers. Spontaneous disappearance was log-linear in 12/23 infants, providing for calculation of an endogenous Kt which correlated significantly (P < 0.01) with the exogenous Kt determined after the dextrose injection, r = 0.74. Hypoglycemia < 20 mg/dl occurred in 4/23 infants, and was identified during the spontaneous glucose disappearance (3 infants) and/or predicted by an endogenous Kt greater than or equal to 3.0%/min (2 infants). There was also a significant inverse correlation (P < 0.01) of the lowest blood glucose obtained within the first 24 h of life with the endogenous Kt, r = 0.61. There was no correlation of the endogenous or exogenous Kt, lowest blood glucose or hypoglycemia with White's classification of the maternal diabetes, diabetic control during pregnancy, the maternal blood glucose at delivery or the cord blood glucose. These data indicate that determination of spontaneous glucose disappearance within the first 90 min of life is useful in identifying infants of diabetic mothers with hypoglycemia or those who will subsequently develop hypoglycemia.

Blood Glucose↗
PubMed1976

A comparative analysis of compartmentation of metabolism in the dorsal root ganglion and ventral spinal cord gray using [U-14C]glucose, [2-14C]glucose, [6-14C]glucose, [3,4-14C]glucose, NaH14CO3, and [2-14C]pyruvate.

A detailed temporal comparison of glucose metabolism, in the production of glutamate and glutamine as well as aspartate and alamine, was conducted in order to further define the uniqueness of the dorsal root ganglion compared to the ventral spinal cord gray. Experiments with injected labeled NaHCO3 and pyruvate were used in an attempt to clarify certain aspects of the above results with different [14C]glucose precursors. The glutamine/glutamate relative specific activity ratio (RSA) was consistently lower in the ganglion than in the ventral spinal cord gray, as was also true for glutamate specific activity from the same amount of injected [14C]glucose. The ganglion is characterized by a high level of alanine production from glucose and pyruvate. The NaH14CO3 experiments suggest that CO2 fixation from [3,4-14C]-glucose in the dorsal rool ganglion resul .ts in a higher glutamine/glutamate RSA when compared to results using either [6-14C] or [2-14C]glucose.

Alanine↗
PubMed1980

Cause of glucose oscillations during glucose infusion: periodic variation in glucose uptake.

Constant infusion of glucose (10 mg . kg-1 . min-1) into conscious, intact dogs induced oscillations in the plasma concentrations of glucose and insulin. Glucose rose from basal (98 +/- 1 mg/dl) and, after 3 h, entered oscillations that persisted until the end of the 9-h glucose infusion. Between 240 and 540 min, glucose fluctuated by +/- 17 mg/dl about a mean value of 143 +/- 2 mg/dl; frequency of the glucose oscillation was 0.54 +/- 0.03 cycles/h. During the same time interval, insulin increased from basal 13 +/- 2 mu U/ml to mean 46 +/- 4 mu U/ml. Insulin oscillated at an amplitude (peak-to-peak) of 48 mu U/ml, with frequency not different from that of glucose (0.60 +/- 0.09 cycles/h). The oscillation in glucose "led" the insulin oscillation by 22 +/- 5 min. In three animals, [2-3H]glucose was infused along with unlabeled glucose during oscillations, and it was determined that almost all (98%) of the glucose appearance was from the exogenous infusion. Thus varying endogenous glucose production was ruled out as a contributory factor to the glucose oscillation. Total glucose uptake (Rd) fluctuated periodically at the same frequency as glucose and insulin (0.56 +/- 0.05 cycles/h) and with a large amplitude (Rd mean = 248 mg/min; peak-to-peak amplitude = 85 mg/min). Direct splanchnic balance measurements were made in the interval 240-540 min to determine the specific contributions of splanchnic (Rds) and peripheral glucose uptake (Rdp) to the oscillation in total Rd. Peripheral uptake oscillated in phase with plasma insulin and accounted for 80% (57.5 g) of total Rd. The splanchnic bed (presumably liver) sequestered 20% (14.1 g) of infused glucose, and Rds varied in phase with plasma glucose. The liver extracted 5.6 +/- 0.3% of the total amount of glucose presented to it in the 5-h interval of observation. It is concluded that a) large fluctuations in peripheral glucose utilization are responsible for the observed periodicities in glucose concentration; b) peripheral uptake fluctuations result from periodic bursts in insulin secretion; c) during glucose infusion, glucose is the primary moment-to-moment regulator of hepatic glucose uptake, whereas insulin is the principal regulator of peripheral glucose utilization.

Animals↗
PubMed1995

Insulin and glucose modulate glucose transporter messenger ribonucleic acid expression and glucose uptake in trophoblasts isolated from first-trimester chorionic villi.

OBJECTIVE: Our purpose was to determine the effects of insulin and glucose on glucose transport and expression of GLUT1 glucose transporter messenger ribonucleic acid in first-trimester human trophoblast-like cells. STUDY DESIGN: First-trimester human trophoblast-like cells were maintained as a continuous cell line. For 2[3H]deoxy-D-glucose uptake and messenger ribonucleic acid studies the cells were incubated in the presence or absence of insulin (10(-7) to 10(-11) mol/L) or D-glucose (0 to 50 mmol/L) for 0 to 24 hours. Glucose transport was measured by incubating cells with 0.1 mmol/L 2[3H]deoxy-D-glucose for 5 minutes. Specific uptake was determined by incubating companion cultures with 10 mumol/L cytochalasin B. The cells were then solubilized with sodium hydroxide and the radioactivity counted. Data were expressed as nanomoles of 2[3H]deoxy-D-glucose transported per milligram of protein per 5 minutes and analyzed by one-way analysis of variance with post hoc testing by the method of Tukey. GLUT1 messenger ribonucleic acid was measured by Northern blotting of total ribonucleic acid samples hybridized to a phosphorus 32-labeled complementary deoxyribonucleic encoding the rat GLUT1 glucose transporter. As a control for loading efficiency, blots were stripped and rehybridized to a 40-mer phosphorus 32-labeled beta-actin oligonucleotide probe. RESULTS: Insulin treatment resulted in a dose-dependent increase in the transport of 2[3H]deoxy-D-glucose at 24 hours (p < 0.001 at 10(-7) mol/L). This change was first detected at 12 hours of incubation. These data closely paralleled the insulin-induced increase in GLUT1 messenger ribonucleic acid seen in Northern blots. In contrast to insulin, increasing concentrations of D-glucose did not change the transport of 2[3H]deoxy-D-glucose. However, when cells were incubated in low concentrations of D-glucose (0 or 1 mmol/L), an enhancement in the uptake of 2[3H]deoxy-D-glucose (p < 0.001) was observed. Kinetic studies indicated that D-glucose augmentation of 2[3H]eoxy-D-glucose uptake was significant at 9 hours (p < 0.05). The effects of D-glucose on GLUT1 messenger ribonucleic acid expression paralleled the uptake of 2[3H]deoxy-D-glucose, although the modulation of GLUT1 messenger ribonucleic acid levels by glucose was much less pronounced than in insulin-treated cells. CONCLUSION: Although it has been assumed that the placenta has a limited role in influencing glucose transport to the fetus, our in vitro data demonstrate that both insulin and glucose can modulate glucose transport at the cellular level of the placental trophoblast. Thus maternal insulin and glycemic status may influence the expression of GLUT1, the major trophoblast glucose transporter protein, therefore directly affecting first-trimester placental glucose transport. These in vitro data may help explain the association between maternal glucose abnormalities and impaired fetal development during the first trimester when placental GLUT1 messenger ribonucleic acid expression is at its peak.

Analysis of Variance↗
PubMed1999

Normalization of glucose entry under the high glucose condition by phlorizin attenuates the high glucose-induced morphological and functional changes of cultured bovine retinal pericytes.

We previously reported that sodium-dependent glucose uptake is present in bovine retinal pericytes and that phlorizin normalizes its glucose consumption under high glucose conditions. To clarify the effect of phlorizin on morphological and functional change of retinal pericytes under high glucose conditions, retinal pericytes were incubated in media with 5 mM glucose, 30 mM glucose, and 30 mM glucose plus 0.2 mM phlorizin for 7 days. The diameter of cells in the concentrations of glucose more than 10 mM were significantly larger than those in 5 mM glucose and 30 mM glucose plus phlorizin. Glucose, sorbitol and fructose contents of the cells in 30 mM glucose were significantly increased compared with those in 5 mM glucose, and were normalized by phlorizin. Thymidine uptake in the concentrations of glucose more than 20 mM was significantly decreased compared with that in 5 mM glucose. Myoinositol uptake, and DNA in 30 mM glucose were significantly reduced, and were normalized with phlorizin. Myoinositol content in 30 mM glucose was the same as that in 5 mM glucose, but was significantly decreased by phlorizin. The ratios of glucose to sorbitol or fructose in 30 mM glucose were significantly decreased, compared with those in 5 mM glucose and 30 mM glucose plus phlorizin. Therefore, the cellular enlargement and decreased DNA synthesis in cultured bovine retinal pericytes with abnormal glucose metabolism under high glucose conditions are attenuated by phlorizin, independent of the cellular myoinositol content.

Animals↗
PubMed1981

Effects of plasma glucose concentration on glucose utilization and glucose clearance in normal man.

Glucose clearance (glucose utilization divided by plasma glucose) is commonly used to assess glucose utilization under conditions in which plasma glucose concentrations vary. The validity of this practice requires that glucose clearance itself be independent of plasma glucose concentration. The present studies were, therefore, undertaken to determine the relationship between glucose clearance and plasma glucose concentration in man. Using the glucose clamp technique, rates of glucose utilization (measured isotopically with 3-3H-glucose) and glucose clearance were determined in 5 normal volunteers at steady-state plasma glucose concentrations of approximately 60, 95, 130, and 165 mg/dl, while plasma insulin concentrations were maintained constant (approximately 18 microU/ml) by infusion of insulin and somatostatin. Despite virtually identical 0.4 mg X kg-1 X min-1 increments in glucose utilization for each 35-mg/dl increment in plasma glucose, glucose clearance decreased as a function of plasma glucose concentration (r = -0.85, P less than 0.001). These results indicate that glucose clearance is not independent of changes in plasma glucose concentration and, thus, use of glucose clearance to evaluate glucose utilization of differing plasma glucose concentration is not valid. Whether this conclusion also applies to similar use of clearance for other substrates remains to be determined.

Adult↗
PubMed1988

Relationship of hepatic glucose uptake to intrahepatic glucose concentration in fasted rats after glucose load.

Glucose concentration gradients across the liver and hepatic blood flow were measured to characterize the relationship of hepatic glucose uptake to hepatic glucose concentration for 240 min after administration of a large oral glucose load to fasted rats. Extraction of glucose occurred only transiently, from 20 to 80 min after glucose administration. The liver changed from net glucose output to net glucose removal only when the intracellular hepatic glucose concentration exceeded 12.5 mumol/ml water. Even when arteriovenous glucose concentrations gradients were compatible with net direct hepatic uptake of glucose, the hepatic glucose concentration always exceeded the inflow glucose concentration. These data indicate that direct glucose uptake occurred against a concentration gradient when the liver is considered as a whole. The hepatic intracellular-to-extracellular glucose concentration gradient changed very little, suggesting that this is not being regulated by glucose, insulin, or other effectors. The mechanism by which the hepatic glucose concentration and net hepatic glucose uptake versus output are coordinated is unknown. The rate of glycogen synthesis was linear for 120 min after administration of the glucose load. This occurred in the presence of direct uptake of glucose early in the time course and later in the presence of net glucose output by the liver. Net direct uptake of glucose by the liver could account for, at most, 37-55% of the glycogen formed. Fractional extraction of both lactate and alanine decreased after glucose was given, but net hepatic uptake of these metabolites could account for 33-49 and 7-10%, respectively, of the glycogen formed, depending on plasma versus blood water flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1998

Glucose repression in Saccharomyces cerevisiae is related to the glucose concentration rather than the glucose flux.

Glucose plays an important regulatory role in the yeast Saccharomyces cerevisiae, which is mostly reflected at the transcriptional level by glucose repression. The signal that initiates glucose repression is unknown, but data indicate that it is located at or above the level of glucose 6-phosphate, suggesting the involvement of either the intracellular or extracellular glucose concentration or the glucose flux in triggering glucose repression. We have investigated the role of the glucose flux and the extracellular glucose concentration in glucose repression by growing the cells in continuous culture under nitrogen limitation. By a step-wise increase in the glucose feed concentration, the glucose flux and extracellular glucose concentrations were modulated in an accurate way. Furthermore, the glucose flux and glucose concentrations were modulated independently of each other by increasing the dilution rate or by the use of fructose as a substrate. Using these approaches we demonstrate that glucose repression is related to the extracellular (or intracellular) glucose concentration rather than the glucose flux. At external glucose concentrations lower than 14 mM, glucose repression of SUC2 gene transcription was not triggered, whereas glucose repression of this gene was activated when the glucose concentration exceeded 18 mM. A comparable effect was observed for the glucose-repressible carbon source fructose.

Dose-Response Relationship, Drug↗
PubMed1984

Effectiveness of glycosylated hemoglobin, fasting plasma glucose, and a single post load plasma glucose level in population screening for glucose intolerance.

Five shortcut methods of population screening for glucose intolerance (impaired glucose tolerance and non-insulin-dependent diabetes mellitus) were assessed for effectiveness: 1) glycosylated hemoglobin concentration (HbA1), 2) fasting plasma glucose level, 3) combinations of fasting plasma glucose and HbA1, 4) plasma glucose one hour post oral glucose load, and 5) plasma glucose two hour post oral glucose load. In a sample of the Israeli Jewish population aged 40-70 years, 2040 participants in the Israel Study of Glucose Intolerance, Obesity and Hypertension, who were not known to be diabetic, underwent an oral glucose tolerance test based on three blood samples (fasting, one hour, and two hour post oral glucose load). In 1058 of the subjects, HbA1 was also measured, and was found to increase significantly (P less than 0.001) with increasing glucose intolerance, but with extensive overlap of ranges, even between normals and newly found diabetics. Fasting plasma glucose was more effective than HbA1 in screening for both impaired glucose tolerance and diabetes by its higher specificity and predictive value of a positive test at comparable sensitivity levels. Combinations of HbA1 and fasting plasma glucose did not improve prediction over fasting plasma glucose alone. As observed in other studies, the screening effectiveness of fasting plasma glucose was also unsatisfactory, either post load glucose level being more effective. Plasma glucose level two hour post load was better for detection of diabetes alone. Plasma glucose level one hour post load was more effective at detecting the total group of glucose intolerance, but did not discriminate well between impaired tolerance and diabetes. A cost-risk-benefit evaluation suggests that a full three-sample oral glucose tolerance test is the best method in screening for both intolerance categories.

Adult↗
PubMed1982

Intraportal glucose infusion matched to oral glucose absorption. Lack of evidence for "gut factor" involvement in hepatic glucose storage.

These studies were designed to test whether a putative gastrointestinal factor (separate from that stimulating insulin release) is involved in the enhancement of liver glycogen storage during oral glucose ingestion. To do this, we compared net hepatic glucose uptake in conscious dogs, following oral glucose administration, with hepatic uptake during intraportal glucose infusion. The rate of intraportal glucose infusion was calculated to match the time course of gut glucose absorption in the oral administration experiments. In control studies, intragastric instillation of tap water [90 +/- 2.4 (SE) in four dogs had no effect on basal rates of gastrointestinal (GI) glucose uptake (16 +/- 1 mg/min) oe hepatic glucose production (97 +/- 3 mq/min). Net basal GI lactate production was equal to GI glucose utilization (P greater than 0.1); glycolytic conversion of glucose to lactate accounted for all basal GI glucose utilization. In oral experiments, gastric instillation of 1.2 g/kg glucose (N = 8) caused GI glucose absorption to increase within 5 min (P less than 0.01). Net glucose absorption from the gut was maximal (355 1.55 mg/min) at 60 min, and was complete at 165-240 min (mean = 186 min). During absorption, liver switched from production to net uptake by 30 min (P less than 0.01); production was resumed by 3 h. Total glucose taken up by liver was 7.19 +/- 1.8 g (23% oral load). No net metabolism of the instilled glucose to lactate occurred during absorption; GI lactate production was the same during absorption (13.0 +/- 5.0 mg/min) as before glucose instillation (11.2 +/- 2.0 mg/min; P greater than 0.45). In intraportal experiments, intraportal glucose infusion (total = 1.09 g/kg) induced liver to take up glucose by 15 min (P less than 0.01); total hepatic uptake (4.6 +/- 1.5 g) was not significantly different from the oral experiments (P greater than 0.15). Also, nonsplanchnic glucose uptake was the same in the oral (25.1 +/- 2.2) and intraportal (25.2 +/- 1.4) studies. The lack of difference between hepatic and extrahepatic fates of administered glucose with oral and intraportal administration indicates that no putative gut factor need be invoked to explain hepatic glycogen deposition during oral glucose, and it seems probable that no such factor exists in the dog.

Administration, Oral↗
PubMed1986

Increased glucose turnover and glucose cycling in acromegalic patients with normal glucose tolerance.

To characterize the diabetogenic effects of growth hormone, we simultaneously measured glucose turnover with 2-3H- and 6-3H-glucose in six acromegalic patients with normal fasting blood glucose and oral glucose tolerance tests. Eight healthy volunteers served as controls. All subjects were studied under both basal conditions and during glucose infusion (2 mg X kg-1 X min-1). We determined true glucose production and irreversible glucose uptake using 6-3H-glucose and glucose cycling (difference between 2-3H- and 6-3H-glucose). After an overnight fast, glucose production was higher than normal in the acromegalic patients (2.18 +/- 0.15 vs 1.85 +/- 0.03 mg X kg-1 X min-1, p less than 0.05) despite hyperinsulinaemia. The metabolic clearance rate was normal. During the glucose infusion, glucose production was not suppressed as effectively in the acromegalic patients as in controls nor was glucose uptake augmented, while metabolic clearance rate was decreased. In acromegaly, basal glucose cycling was increased (0.44 +/- 0.08 vs 0.25 +/- 0.07 mg X kg-1 X min-1, p less than 0.05). Furthermore cycling of endogenous glucose measured during glucose infusion was also augmented (0.41 +/- 0.05 vs 0.24 +/- 0.05 mg X kg-1 X min-1, p less than 0.05). Hence the increase of glucose cycling (70%) was much more pronounced than that of glucose production (17%). In conclusion, small defects in glucose metabolism in acromegaly can be detected with sensitive tracer methods. These derangements are confined to the liver under fasting conditions, but are of both hepatic and extrahepatic origin during glucose loading.

Acromegaly↗
PubMed1998

Both positive and negative portal venous and hepatic arterial glucose gradients stimulate hepatic glucose uptake after the same amount of glucose is infused into the splanchnic bed in conscious dogs.

We studied the effects of both positive and negative portal venous and hepatic arterial glucose gradients on hepatic glucose uptake after the same amount of glucose was administered into the portal vein and/or hepatic artery. Studies were performed on eight unrestrained conscious dogs with catheters in the portal vein, hepatic vein, gastroduodenal artery, superior mesenteric vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. Glucose was infused as follows: protocol 1, 55.6 micromol/kg/min into the portal vein for the first 90 minutes; protocol 2, 27.8 micromol/kg/min into both the portal vein and hepatic artery for the next 90 minutes; and protocol 3, 55.6 micromol/kg/min into the hepatic artery for the last 90 minutes. The portal venous and hepatic arterial plasma glucose gradient was 2.1+/-0.3, -3.0+/-0.5, and -7.1+/-0.6 mmol/L, the rate of hepatic glucose uptake divided by the administered glucose load was 46%+/-11%, 42%+/-10%, and 57%+/-8%, net hepatic glucose uptake was 25.4+/-5.9, 23.5+/-5.6, and 31.6+/-4.6 micromol/kg/min; and the fractional hepatic extraction of glucose was 10.7%+/-2.2%, 11.6%+/-2.5%, and 15.0%+/-2.1%, respectively (mean+/-SEM of three points at 60, 75, and 90 minutes in each protocol). The rate of hepatic glucose uptake divided by the administered glucose load, net hepatic glucose uptake, and fractional hepatic extraction of glucose did not change significantly despite the various portal venous and hepatic arterial glucose gradients. We also studied the effect of the same amount of intraportal glucose infusion for 240 minutes on net hepatic glucose uptake. From 60 to 240 minutes, net hepatic glucose uptake did not change significantly. In conclusion, the liver took up a large amount of glucose administered into the portal vein and/or hepatic artery, regardless of positive or negative portal venous and hepatic arterial glucose gradients. Augmentation of hepatic glucose uptake is not dependent on the signal of the positive or negative portal venous and hepatic arterial glucose gradient.

Animals↗
PubMed2003

A Saccharomyces cerevisiae mutant unable to convert glucose to glucose-6-phosphate accumulates excessive glucose in the endoplasmic reticulum due to core oligosaccharide trimming.

D-Glucose is the preferred carbon and energy source for most eukaryotic cells. Immediately following its uptake, glucose is rapidly phosphorylated to glucose-6-phosphate (Glc-6-P). The yeast Saccharomyces cerevisiae has three enzymes (Hxk1p, Hxk2p, and Glk1p) that convert glucose to Glc-6-P. In the present study, we found that yeast mutants lacking any two of these enzymes retain the ability to efficiently convert glucose to Glc-6-P and thus maintain a low level of cellular glucose. However, a mutant strain lacking all three glucose-phosphorylating enzymes contained up to 225-fold more intracellular glucose than normal. Drugs that inhibit the synthesis or the trimming of the lipid-linked core oligosaccharide Glu(3)Man(9)GlcNac(2) effectively reduced the accumulation of glucose. Similarly, mutations that block the addition of glucose residues to the core oligosaccharide moiety, such as alg5Delta or alg6Delta, also diminished glucose accumulation. These results indicate that the intracellular glucose accumulation observed in the glucose phosphorylation mutant results primarily from the trimming of glucose residues from core oligosaccharide chains within the endoplasmic reticulum (ER). Consistent with this conclusion, both [(14)C]glucose exchange and subcellular fractionation experiments indicate that much of the accumulated glucose is retained within an intracellular compartment, suggesting that the efficient transport of glucose from the ER to the cytosol in yeast may be coupled to its rephosphorylation to Glc-6-P. The high level of cellular glucose was associated with an increased level of protein glycation and the release of glucose into the culture medium via its transit through the secretory pathway. Finally, we also found that the accumulation of glucose may lead to a subtle alteration in ion homeostasis, particularly Ca(2+) uptake. This suggests that this mutant strain may serve as a useful model to study the consequences of excessive glucose accumulation and protein glycation.

Culture Media↗
PubMed1991

Intraportal glucose delivery enhances the effects of hepatic glucose load on net hepatic glucose uptake in vivo.

Although the importance of the hepatic glucose load in the regulation of liver glucose uptake has been clearly demonstrated in in vitro systems, the relationship between the hepatic glucose load and hepatic glucose uptake has yet to be defined in vivo. Likewise, the effects of the route of glucose delivery (peripheral or portal) on this relationship have not been explored. The aims of the present study were to determine the relationship between net hepatic glucose uptake (NHGU) and the hepatic glucose load in vivo and to examine the effects of the route of glucose delivery on this relationship. NHGU was evaluated at three different hepatic glucose loads in 42-h fasted, conscious dogs in both the absence (n = 7) and the presence (n = 6) of intraportal glucose delivery. In the absence of intraportal glucose delivery and in the presence of hepatic glucose loads of 50.5 +/- 5.9, 76.5 +/- 10.0, and 93.6 +/- 10.0 mg/kg/min and arterial insulin levels of approximately 33 microU/ml, NHGU was 1.16 +/- 0.37, 2.78 +/- 0.82, and 5.07 +/- 1.20 mg/kg/min, respectively. When a portion of the glucose load was infused into the portal vein and similar arterial insulin levels (approximately 36 microU/ml) and hepatic glucose loads (52.5 +/- 4.5, 70.4 +/- 5.6, and 103.6 +/- 18.4 mg/kg/min) were maintained, NHGU was twice that seen in the absence of portal loading (3.77 +/- 0.40, 4.80 +/- 0.59, and 9.62 +/- 1.43 mg/kg/min, respectively). Thus, net hepatic glucose uptake demonstrated a direct dependence on the hepatic glucose load that did not reach saturation even at elevations in the hepatic glucose load of greater than three times basal. In addition, the presence of intraportal glucose delivery increased net hepatic glucose uptake apparently by lowering the threshold at which the liver switched from net glucose output to net glucose uptake.

Animals↗