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Willy Malaisse - One of the best experts on this subject based on the ideXlab platform.
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Mathematical modelling of alpha- and beta-D-Glucose metabolism in pancreatic islets exposed to equilibrated D-Glucose.
International journal of molecular medicine, 2004Co-Authors: Willy Malaisse, Abdullah SenerAbstract:Based on the measurement of 3HOH generation from the alpha- and beta-anomer of D-[2-3H]glucose and D-[5-3H] glucose by rat pancreatic islets, it was recently proposed that alpha-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between hexokinase isoenzymes and phosphoglucoisomerase. Taking into account the results of such measurements, the present study aims at defining a model for the metabolism of alpha- and beta-D-Glucose in islets exposed to 2.8 or 8.3 mM equilibrated D-Glucose. It is proposed that, whilst keeping the activity of free phosphoglucoisomerase at its physiological value, all available experimental data can be adequately reproduced in a model in which all molecules of alpha-D-Glucose 6-phosphate, whether unlabelled or tritiated on their C2 carbon atom, undergo, without isotopic discrimination, the postulated enzyme-to-enzyme channelling process. In such a model, the fractional intermolecular transfer of tritium at the phosphoglucoisomerase level amounts to 26%, suggesting that the intrinsic catalytic properties of the enzyme may be slightly different in the proposed metabolon than that prevailing for the unbound enzyme. These findings thus afford further support to the concept that alpha-D-Glucose 6-phosphate, as distinct from beta-D-Glucose 6-phosphate, is tunnelled, in rat pancreatic islets, in the sequence of reactions catalyzed by hexokinase isoenzymes, phosphoglucoisomerase and, possibly, phosphofructokinase.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and Cellular Biochemistry, 2004Co-Authors: Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah Sener, Willy MalaisseAbstract:It was recently proposed that α-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4°C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in β-D-[5-3H]glucose, as compared to α-D-[5-3H]glucose, conversion to 3HOH and an increase in the β/α ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the β/α ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, α- and β-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to α-D-Glucose but not significantly different from unity in the presence of β-D-Glucose. These findings emphasize the relevance of α-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
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Metabolism of D-Glucose anomers in rat pancreatic islets exposed to equilibrated D-Glucose.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2004Co-Authors: Willy Malaisse, Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah SenerAbstract:This study aims at establishing the contribution of alpha- and beta-D-Glucose to the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 - (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were incubated for 60 min at 4 degrees C in the presence of equilibrated D-Glucose (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-Glucose labelled with tritium on either the C (2) or C (5) of the hexose. Relative to their respective concentrations, (3)HOH generation from the anomers labelled with tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to each anomer separately. The relative contributions of each anomer to the total generation of (3)HOH was also close to the theoretical values derived from mathematical models for the catabolism of D-Glucose at anomeric equilibrium in rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and D-[5 - (3)H]glucose. Thus, even in islets exposed to D-Glucose at anomeric equilibrium, the metabolic fate of alpha-D-Glucose differs vastly from that of beta-D-Glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes, especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D-Glucose 6-phosphate.
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Underestimation of D-Glucose utilisation as judged from the conversion of D-[3-^3H]glucose to ^3HOH
Diabetologia, 2002Co-Authors: A. Sener, M.-h. Giroix, Willy MalaisseAbstract:Aims/hypothesis. The conversion of D -[3-^3H]glucose to ^3HOH is currently measured to assess D -glucose utilisation. The validity of such a procedure was re-evaluated. Methods. The conversion of D -[3-^3H]glucose and D -[5-^3H]glucose to ^3HOH was measured in rat pancreatic islets, parotid cells and erythrocytes. The tritiation of lipids were also examined in islets exposed to D -[3-^3H]glucose or D -[5-^3H]glucose. Results. In rat pancreatic islets and parotid cells, but not in rat erythrocytes, the generation of ^3HOH from D -[3-^3H]glucose underestimates the rate of D -glucose utilisation, this being apparently attributable to a partial escape from detritiation of [1-^3H]glycerone-3-phosphate. Such an escape phenomenon resulted in a higher tritiation of lipids in pancreatic islets exposed to D -[3-^3H]glucose, rather than D -[5-^3H]glucose. Its relative extent was affected by a number of environmental factors such as the cell type under consideration, the metabolic status of the animals, and the extracellular concentration of D -glucose. Conclusion/interpretation. These findings impose a reservation on the use of D -[3-^3H]glucose conversion to ^3HOH as a tool to assess the utilisation of the hexose in some cell types.
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Insulinotropic Action of α-D-Glucose Pentaacetate: Metabolic Aspects
Molecular genetics and metabolism, 1998Co-Authors: Abdullah Sener, Francine Malaisse-lagae, M M Kadiata, Nils Welsh, Willy MalaisseAbstract:Abstract The metabolism and metabolic effects of α- d -glucose pentaacetate were investigated in isolated rat pancreatic islets. Several findings were compatible with the view that the insulinotropic action of α- d -glucose pentaacetate is causally related to its capacity to act as a fuel in the islet B-cell. First, the ester was efficiently taken up and hydrolyzed with resulting accumulation of d -glucose in the islet cells. Second, the conversion of α- d -[5-3H]glucose pentaacetate to3HOH and that of α- d -[U-14C]glucose pentaacetate to14CO2exceeded those found at an equimolar concentration (1.7 mM) of d -glucose and were both inhibited by 2-deoxy- d -glucose (16.7 mM). Last, the ester inhibited the catabolism of both exogenous d -glucose or endogenous fatty acids. Yet, an apparent dissociation between the metabolic and secretory responses to the ester was suggested by the failure of α- d -glucose pentaacetate to increase O2uptake by the islets. Moreover, there were striking differences between the catabolism of the ester and that of unesterified d -glucose, such as a much higher intracellular d -glucose content and an insensitiveness to the inhibitory action of d -mannoheptulose in islets exposed to α- d -glucose pentaacetate. Likewise, the ratio between hexose oxidation and utilization was lower for α- d -glucose pentaacetate than for unesterified d -glucose in islets concomitantly exposed to the hexose and its ester. It is proposed, therefore, that the insulinotropic action of α- d -glucose pentaacetate, although probably linked to the intracellular generation of d -glucose from the ester, may not involve the same coupling process between metabolic and functional events as that currently implied in the process of glucose-stimulated insulin release.
Abdullah Sener - One of the best experts on this subject based on the ideXlab platform.
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Mathematical modelling of alpha- and beta-D-Glucose metabolism in pancreatic islets exposed to equilibrated D-Glucose.
International journal of molecular medicine, 2004Co-Authors: Willy Malaisse, Abdullah SenerAbstract:Based on the measurement of 3HOH generation from the alpha- and beta-anomer of D-[2-3H]glucose and D-[5-3H] glucose by rat pancreatic islets, it was recently proposed that alpha-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between hexokinase isoenzymes and phosphoglucoisomerase. Taking into account the results of such measurements, the present study aims at defining a model for the metabolism of alpha- and beta-D-Glucose in islets exposed to 2.8 or 8.3 mM equilibrated D-Glucose. It is proposed that, whilst keeping the activity of free phosphoglucoisomerase at its physiological value, all available experimental data can be adequately reproduced in a model in which all molecules of alpha-D-Glucose 6-phosphate, whether unlabelled or tritiated on their C2 carbon atom, undergo, without isotopic discrimination, the postulated enzyme-to-enzyme channelling process. In such a model, the fractional intermolecular transfer of tritium at the phosphoglucoisomerase level amounts to 26%, suggesting that the intrinsic catalytic properties of the enzyme may be slightly different in the proposed metabolon than that prevailing for the unbound enzyme. These findings thus afford further support to the concept that alpha-D-Glucose 6-phosphate, as distinct from beta-D-Glucose 6-phosphate, is tunnelled, in rat pancreatic islets, in the sequence of reactions catalyzed by hexokinase isoenzymes, phosphoglucoisomerase and, possibly, phosphofructokinase.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and Cellular Biochemistry, 2004Co-Authors: Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah Sener, Willy MalaisseAbstract:It was recently proposed that α-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4°C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in β-D-[5-3H]glucose, as compared to α-D-[5-3H]glucose, conversion to 3HOH and an increase in the β/α ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the β/α ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, α- and β-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to α-D-Glucose but not significantly different from unity in the presence of β-D-Glucose. These findings emphasize the relevance of α-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
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Metabolism of D-Glucose anomers in rat pancreatic islets exposed to equilibrated D-Glucose.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2004Co-Authors: Willy Malaisse, Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah SenerAbstract:This study aims at establishing the contribution of alpha- and beta-D-Glucose to the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 - (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were incubated for 60 min at 4 degrees C in the presence of equilibrated D-Glucose (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-Glucose labelled with tritium on either the C (2) or C (5) of the hexose. Relative to their respective concentrations, (3)HOH generation from the anomers labelled with tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to each anomer separately. The relative contributions of each anomer to the total generation of (3)HOH was also close to the theoretical values derived from mathematical models for the catabolism of D-Glucose at anomeric equilibrium in rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and D-[5 - (3)H]glucose. Thus, even in islets exposed to D-Glucose at anomeric equilibrium, the metabolic fate of alpha-D-Glucose differs vastly from that of beta-D-Glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes, especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D-Glucose 6-phosphate.
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Insulinotropic Action of α-D-Glucose Pentaacetate: Metabolic Aspects
Molecular genetics and metabolism, 1998Co-Authors: Abdullah Sener, Francine Malaisse-lagae, M M Kadiata, Nils Welsh, Willy MalaisseAbstract:Abstract The metabolism and metabolic effects of α- d -glucose pentaacetate were investigated in isolated rat pancreatic islets. Several findings were compatible with the view that the insulinotropic action of α- d -glucose pentaacetate is causally related to its capacity to act as a fuel in the islet B-cell. First, the ester was efficiently taken up and hydrolyzed with resulting accumulation of d -glucose in the islet cells. Second, the conversion of α- d -[5-3H]glucose pentaacetate to3HOH and that of α- d -[U-14C]glucose pentaacetate to14CO2exceeded those found at an equimolar concentration (1.7 mM) of d -glucose and were both inhibited by 2-deoxy- d -glucose (16.7 mM). Last, the ester inhibited the catabolism of both exogenous d -glucose or endogenous fatty acids. Yet, an apparent dissociation between the metabolic and secretory responses to the ester was suggested by the failure of α- d -glucose pentaacetate to increase O2uptake by the islets. Moreover, there were striking differences between the catabolism of the ester and that of unesterified d -glucose, such as a much higher intracellular d -glucose content and an insensitiveness to the inhibitory action of d -mannoheptulose in islets exposed to α- d -glucose pentaacetate. Likewise, the ratio between hexose oxidation and utilization was lower for α- d -glucose pentaacetate than for unesterified d -glucose in islets concomitantly exposed to the hexose and its ester. It is proposed, therefore, that the insulinotropic action of α- d -glucose pentaacetate, although probably linked to the intracellular generation of d -glucose from the ester, may not involve the same coupling process between metabolic and functional events as that currently implied in the process of glucose-stimulated insulin release.
Ying Zhang - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and Cellular Biochemistry, 2004Co-Authors: Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah Sener, Willy MalaisseAbstract:It was recently proposed that α-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4°C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in β-D-[5-3H]glucose, as compared to α-D-[5-3H]glucose, conversion to 3HOH and an increase in the β/α ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the β/α ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, α- and β-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to α-D-Glucose but not significantly different from unity in the presence of β-D-Glucose. These findings emphasize the relevance of α-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
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Metabolism of D-Glucose anomers in rat pancreatic islets exposed to equilibrated D-Glucose.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2004Co-Authors: Willy Malaisse, Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah SenerAbstract:This study aims at establishing the contribution of alpha- and beta-D-Glucose to the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 - (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were incubated for 60 min at 4 degrees C in the presence of equilibrated D-Glucose (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-Glucose labelled with tritium on either the C (2) or C (5) of the hexose. Relative to their respective concentrations, (3)HOH generation from the anomers labelled with tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to each anomer separately. The relative contributions of each anomer to the total generation of (3)HOH was also close to the theoretical values derived from mathematical models for the catabolism of D-Glucose at anomeric equilibrium in rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and D-[5 - (3)H]glucose. Thus, even in islets exposed to D-Glucose at anomeric equilibrium, the metabolic fate of alpha-D-Glucose differs vastly from that of beta-D-Glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes, especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D-Glucose 6-phosphate.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and cellular biochemistry, 2004Co-Authors: Ying Zhang, A. Sener, Hassan Jijakli, Philippe Courtois, W J MalaisseAbstract:It was recently proposed that alpha-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4 degrees C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in beta-D-[5-3H]glucose, as compared to alpha-D-[5-3H]glucose, conversion to 3HOH and an increase in the beta/alpha ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the beta/alpha ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, alpha- and beta-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to alpha-D-Glucose but not significantly different from unity in the presence of beta-D-Glucose. These findings emphasize the relevance of alpha-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
W J Malaisse - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and cellular biochemistry, 2004Co-Authors: Ying Zhang, A. Sener, Hassan Jijakli, Philippe Courtois, W J MalaisseAbstract:It was recently proposed that alpha-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4 degrees C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in beta-D-[5-3H]glucose, as compared to alpha-D-[5-3H]glucose, conversion to 3HOH and an increase in the beta/alpha ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the beta/alpha ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, alpha- and beta-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to alpha-D-Glucose but not significantly different from unity in the presence of beta-D-Glucose. These findings emphasize the relevance of alpha-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
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Stimulation by hexose esters of lactate production by rat erythrocytes: insensitivity to 3-O-methyl-D-Glucose and inhibition by 2-deoxy-D-Glucose and its tetraacetic ester.
Molecular and cellular biochemistry, 1998Co-Authors: L Ladrière, M M Kadiata, O Kirk, W J MalaisseAbstract:Selected esters of D-Glucose were recently proposed as tools to provide the sugar to cells, whilst bypassing the carrier system for hexose transport across the plasma membrane. In the present study, alpha-D-Glucose pentaacetate, beta-D-Glucose pentaacetate, alpha-D-mannose pentaacetate and, to a lesser extent, 6-O-acetyl-D-Glucose, all tested at a 1.7 mM concentration, were found to increase lactate production above basal value in rat erythrocytes. Over 90 min incubation, the increment in lactate production ranged from about 1.2 (alpha-D-Glucose pentaacetate) to 0.6 (6-O-acetyl-D-Glucose) micromol/microl of erythrocytes. Little or no change in lactate production was observed in cells exposed to beta-L-glucose pentaacetate, alpha-D-Glucose pentaethylsuccinate, alpha-D-galactose pentaacetate or beta-D-galactose pentaacetate. The metabolic response to alpha-D-Glucose pentaacetate was resistant to 3-O-methyl-D-Glucose (10-80 mM) which suppressed, however, that evoked by D-Glucose. D-mannoheptulose (10 mM) virtually failed to affect the response to D-Glucose and its pentaacetate ester. On the contrary, 2-deoxy-D-Glucose (10.6 mM) inhibited to the same relative extent (55% decrease) lactate production in erythrocytes exposed to either unesterified D-Glucose or alpha-D-Glucose pentaacetate. The tetraacetic ester of 2-deoxy-D-Glucose was more efficient than unesterified 2-deoxy-D-Glucose in inhibiting lactate production from alpha-D-Glucose pentaacetate. It is proposed that selected esters of saccharides represent useful tools to bypass defects in hexose transport, and to increase their nutritional or therapeutic efficiency.
Philippe Courtois - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and Cellular Biochemistry, 2004Co-Authors: Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah Sener, Willy MalaisseAbstract:It was recently proposed that α-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4°C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in β-D-[5-3H]glucose, as compared to α-D-[5-3H]glucose, conversion to 3HOH and an increase in the β/α ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the β/α ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, α- and β-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to α-D-Glucose but not significantly different from unity in the presence of β-D-Glucose. These findings emphasize the relevance of α-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
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Metabolism of D-Glucose anomers in rat pancreatic islets exposed to equilibrated D-Glucose.
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 2004Co-Authors: Willy Malaisse, Ying Zhang, Hassan Jijakli, Philippe Courtois, Abdullah SenerAbstract:This study aims at establishing the contribution of alpha- and beta-D-Glucose to the total generation of (3)HOH by rat pancreatic islets exposed to D-[2 - (3)H]glucose or D-[5 - (3)H] glucose at anomeric equilibrium. The islets were incubated for 60 min at 4 degrees C in the presence of equilibrated D-Glucose (2.8 and 8.3 mM) mixed with tracer amounts of either alpha- or beta-D-Glucose labelled with tritium on either the C (2) or C (5) of the hexose. Relative to their respective concentrations, (3)HOH generation from the anomers labelled with tritium on the C (2) or C (5) of the hexose provided beta/alpha ratios comparable to those previously found at both 2.8 and 8.3 mM, when the islets were exposed to each anomer separately. The relative contributions of each anomer to the total generation of (3)HOH was also close to the theoretical values derived from mathematical models for the catabolism of D-Glucose at anomeric equilibrium in rat islets at both 2.8 and 8.3 mM and in the case of both D-[2 - (3)H]glucose and D-[5 - (3)H]glucose. Thus, even in islets exposed to D-Glucose at anomeric equilibrium, the metabolic fate of alpha-D-Glucose differs vastly from that of beta-D-Glucose, the enzyme-to-enzyme channelling between hexokinase isoenzymes, especially glucokinase, and phosphoglucoisomerase being restricted to alpha-D-Glucose 6-phosphate.
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Metabolism of tritiated D-Glucose anomers in rat erythrocytes.
Molecular and cellular biochemistry, 2004Co-Authors: Ying Zhang, A. Sener, Hassan Jijakli, Philippe Courtois, W J MalaisseAbstract:It was recently proposed that alpha-D-Glucose 6-phosphate may undergo enzyme-to-enzyme channelling between glucokinase and phosphoglucoisomerase in rat pancreatic islets. The present study aims at exploring whether a different situation prevails in cells deprived of glucokinase, namely in erythrocytes. At anomeric equilibrium, the ratio between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH was lower in rat erythrocytes incubated for 60 min at 4 degrees C in the presence of 2.8 mM, rather than 8.3 mM, D-Glucose. This coincided with both a greater relative increase in beta-D-[5-3H]glucose, as compared to alpha-D-[5-3H]glucose, conversion to 3HOH and an increase in the beta/alpha ratio for 3HOH generation from D-[5-3H]glucose in response to an increase in the anomeric concentration from 2.8 to 8.3 mM, the suppression of the difference between the beta/alpha ratios for 3HOH generation from D-[2-3H]glucose and D-[5-3H]glucose in the erythrocytes incubated at 8.3 mM, as distinct from 2.8 mM, alpha- and beta-D-Glucose, and a [2-3H]/[5-3H] ratio for 3HOH generation lower than unity in erythrocytes exposed to alpha-D-Glucose but not significantly different from unity in the presence of beta-D-Glucose. These findings emphasize the relevance of alpha-D-Glucose 6-phosphate channelling between hexokinase and phosphoglucoisomerase as a determinant of the difference between D-[2-3H]glucose and D-[5-3H]glucose conversion to 3HOH, and reveal that the regulation of such a tunnelling process by the concentration of the D-Glucose represents, in rat erythrocytes, a mirror image of that observed in rat pancreatic islets. The regulation of this process thus tightly depends on the identity of the hexokinase enzyme mainly responsible for the phosphorylation of D-Glucose in distinct cell types.
