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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The significance of 3HOH generation by cells exposed to D-[2-3H]glucose is reevaluated. It is proposed that such a metabolic variable, rather than being taken as an index of D-glucose phosphorylation, may provide information on the extent of D-glucose 6-phosphate and D-fructose 6-phosphate interconversion in the reaction catalyzed by phosphoglucoisomerase. In order to reach such an information, the total production of 3HOH from D-[2-3H]glucose needs to be corrected for that attributable to either the catabolism of D-[1-3H]fructose 1,6-bisphosphate or the circulation of D-[2-3H]glucose 6-phosphate in the pentose phosphate pathway. A method is introduced which allows for such a correction.
Diabetes Res 1992 Mar
PMID:Significance of 3HOH generation from D-[2-3H]glucose. 128 49

When either rat or human erythrocytes were incubated for 90-180 min in bicarbonate-buffered media prepared in 2H2O rather than 1H2O, the generation of 3HOH from D-[5-3H]glucose, the production of either 14CO2 or 14C-labelled acidic metabolites from D-[U-14C]glucose and the production of L-lactic acid from unlabelled D-glucose were decreased, to a variable extent but, in no case, by more than 30%. Hence, total substitution of 1H2O by 2H2O provides a suitable tool to study by NMR the generation of 2H-enriched L-lactic acid generated from exogenous D-[1-13C]glucose or D-[6-13C]glucose and, hence, to further explore the diabetes-induced alteration of hydrogen isotopes intermolecular transfer in the reaction catalyzed by phosphoglucoisomerase.
Diabetes Res 1992 Jan
PMID:Effect of 2H2O upon D-glucose metabolism in rat and human erythrocytes. 133 14

The fate of D-[2-3H] glucose and D-[5-3H] glucose in pancreatic islets was simulated in models with or without enzyme-to-enzyme tunnelling of hexose 6-phosphates in the glycolytic cascade. Satisfactory values for the recovery of phosphoglucoisomerase activity, for the ratio between unlabelled D-glucose 6-phosphate and D-fructose 6-phosphate, and for the time course of both 3HOH production from D-[2-3H] glucose and tritiated D-fructose 1,6-bisphosphate generation from D-[5-3H] glucose were only reached in models with enzyme-to-enzyme tunnelling, with emphasis on the coupling between phosphoglucoisomerase and phosphofructokinase.
Diabetes Res 1991 Jan
PMID:Hexose metabolism in pancreatic islets (time course of 3HOH production from tritiated D-glucose in models with and without enzyme-to-enzyme tunnelling). 181 93

A mathematical model is designed for the metabolism of D-glucose in erythrocytes under conditions in which the flux through the pentose phosphate pathway accounts for either 5% or 75% of the rate of D-glucose phosphorylation, as indeed observed in the absence or presence of menadione. This model allows to compare the fate of D-[1-1H]glucose and D-[1-2H]glucose, taking into account the isotopic discrimination towards the deuterated hexose in the reactions catalyzed by phosphoglucoisomerase and glucose-6-phosphate dehydrogenase. The study of this model is extended to the fate of tracer amounts of either D-[1-14C]glucose, D-[U-14C]glucose or D-[1-3H]glucose mixed with non-radioactive D-[1-1H]glucose or D-[1-2H]glucose. The fates of D-[1-14C, 1-2H]glucose and D-[U-14C, 1-2H]glucose in this model are also examined. A fair agreement between the data derived from the mathematical model and prior experimental findings is observed, at least as far as the fate of 14C-labelled D-glucose is concerned. The present study illustrates, therefore, the mechanism by which unequal isotopic discrimination in different enzymatic reactions may cause severe misjudgment of metabolic flow when using deuterated and/or tritiated D-glucose as substitute and/or tracer for the protonated hexose.
Diabetes Res 1991 Sep
PMID:Modelling of isotopic discrimination in intact cells. 182 43

A change in either the ionic composition of the extracellular medium or ambient temperature affects not solely the glycolytic flux in rat erythrocytes, but also the extent of D-[1-3H]glucose or D-[2-3H]glucose detritiation relative to D-[5-3H]glucose utilization. Thus, the production of 3HOH from D-[1-3H]glucose and D-[2-3H]glucose, which is mainly attributable to the reactions catalyzed by phosphomannoisomerase and phosphoglucoisomerase, respectively, is inversely related to the net glycolytic flux. Such an inverse relationship is not universal, however. These findings should serve as a warning in the interpretation of radioactive data, since they imply that experimental changes in D-[1-3H]glucose or D-[2-3H]glucose detritiation may occur in the absence of any alteration in unlabelled D-glucose turnover.
Diabetes Res 1990 Dec
PMID:Environmental alteration of 3HOH production from D-[1-3H]glucose, D-[2-3H]glucose and D-[5-3H]glucose by rat erythrocytes. 213 8

Incubation of yeast phosphoglucoisomerase for 14 days at a high concentration (100 mM) of D-glucose was found to cause the non-enzymatic glycation of the enzyme. The kinetic properties of the glycated and control enzymes were similar in terms of specific activity, affinity for D-glucose 6-phosphate, isotopic discrimination between D-(U-14C) glucose 6-phosphate and D-(2-3H) glucose 6-phosphate, intramolecular 3H transfer from the latter substrate, and anomeric specificity. It is proposed that the quantitation of glycated phosphoglucoisomerase in distinct cell types may be used as an index for the non-enzymatic glycation of cytosolic proteins.
Diabetes Res 1989 Dec
PMID:Non-enzymatic glycation of phosphoglucoisomerase. 270 Jan 52

The activities of enzymes of the glycolytic route, the pentose phosphate pathway and NADPH-linked enzymes have been measured in the kidneys of genetically obese (ob/ob) mice and their lean litter mates. The renal content of glucose 6-phosphate (G6P), fructose 6-phosphate (F6P), fructose 1,6-bisphosphate (Fru-1,6-P2) and fructose 2,6-bisphosphate (Fru-2,6-P2) were also measured. Increases were found in hexokinase and enolase with an upward trend in pyruvate kinase in the ob/ob mouse kidney; a significant decline in malic enzyme was also seen. The renal content of G6P and Fru-1,6-P2 increased. There was no renal hypertrophy despite a degree of hyperglycaemia, which was, however, considerably below that observed in experimental diabetes. Comparison of the renal changes in the hyperglycaemic-hyperinsulinaemic ob/ob mice with the hyperglycaemic-hypoinsulinaemic diabetic group showed two distinct groupings. Firstly, changes which were similar in the two groups included: increases in hexokinase, G6P and Fru-1,6-P2, and a decrease in malic enzyme. Secondly, opposite changes were seen in enolase and in enzymes at the G6P crossroads, phosphoglucose isomerase and phosphoglucomutase. The elevated hexokinase and G6P in both ob/ob and diabetic groups may be involved in the eventual accumulation of basement membrane material in the glomerulus which is a common feature of the two conditions.
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PMID:Regulation of pathways of glucose metabolism in the kidney. The activity of the pentose phosphate pathway, glycolytic route and the regulation of phosphofructokinase in the kidney of lean and genetically obese (ob/ob) mice; comparison with effects of diabetes. 297 63

1. Measurements were made of the activities of nine glycolytic enzymes in epididymal adipose tissues obtained from rats that had undergone one of the following treatments: starvation; starvation followed by re-feeding with bread or high-fat diet; feeding with fat without preliminary starvation; alloxan-diabetes; alloxan-diabetes followed by insulin therapy. 2. In general, the activities of the glycolytic enzymes of adipose tissue, unlike those of liver, were not greatly affected by the above treatments. 3. The ;key' glycolytic enzymes, phosphofructokinase and pyruvate kinase, were generally no more adaptive in response to physiological factors than other glycolytic enzymes such as glucose phosphate isomerase, fructose diphosphate aldolase, triose phosphate isomerase, glycerol 3-phosphate dehydrogenase, phosphoglycerate kinase and lactate dehydrogenase. 4. Adiposetissue pyruvate kinase did not respond to feeding with fat in a manner similar to the liver enzyme. 5. Glyceraldehyde phosphate dehydrogenase had a behaviour pattern unlike the other eight glycolytic enzymes studied in that its activity was depressed by feeding with fat and was not restored to normal by re-feeding with a high-fat diet after starvation. These results are discussed in relation to the requirements of adipose tissue for glycerol phosphate in the esterification of fatty acids. 6. A statistical analysis of the results permitted the writing of linear equations describing the relationships between the activities of eight of the enzymes studied. 7. Evidence is presented for the existence of two constant-proportion groups amongst the enzymes studied, namely (i) glucose phosphate isomerase, phosphoglycerate kinase and lactate dehydrogenase, and (ii) triose phosphate isomerase, fructose diphosphate aldolase and pyruvate kinase. 8. Mechanisms for maintaining the observed relationships between the activities of the enzymes in the tissue are discussed.
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PMID:The effect of dietary and hormonal conditions on the activities of glycolytic enzymes in rat epididymal adipose tissue. 424 55

1. Measurements were made of the non-oxidative reactions of the pentose phosphate cycle in liver (transketolase, transaldolase, ribulose 5-phosphate epimerase and ribose 5-phosphate isomerase activities) in a variety of hormonal and nutritional conditions. In addition, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were measured for comparison with the oxidative reactions of the cycle; hexokinase, glucokinase and phosphoglucose isomerase activities were also included. Starvation for 2 days caused significant lowering of activity of all the enzymes of the pentose phosphate cycle based on activity in the whole liver. Re-feeding with a high-carbohydrate diet restored all the enzyme activities to the range of the control values with the exception of that of glucose 6-phosphate dehydrogenase, which showed the well-known ;overshoot' effect. Re-feeding with a high-fat diet also restored the activities of all the enzymes of the pentose phosphate cycle and of hexokinase; glucokinase activity alone remained unchanged. Expressed as units/g. of liver or units/mg. of protein hexokinase, glucose 6-phosphate dehydrogenase, transketolase and pentose phosphate isomerase activities were unchanged by starvation; both 6-phosphogluconate dehydrogenase and ribulose 5-phosphate epimerase activities decreased faster than the liver weight or protein content. 2. Alloxan-diabetes resulted in a decrease of approx. 30-40% in the activities of 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase and transketolase; in contrast with this glucose 6-phosphate dehydrogenase, transaldolase and phosphoglucose isomerase activities were unchanged. Treatment of alloxan-diabetic rats with protamine-zinc-insulin for 3 days caused a very marked increase to above normal levels of activity in all the enzymes of the pentose phosphate pathway except ribulose 5-phosphate epimerase, which was restored to the control value. Hexokinase activity was also raised by this treatment. After 7 days treatment of alloxan-diabetic rats with protamine-zinc-insulin the enzyme activities returned towards the control values. 3. In adrenalectomized rats the two most important changes were the rise in hexokinase activity and the fall in transketolase activity; in addition, ribulose 5-phosphate epimerase activity was also decreased. These effects were reversed by cortisone treatment. In addition, in cortisone-treated adrenalectomized rats glucokinase activity was significantly lower than the control value. 4. In thyroidectomized rats both ribose 5-phosphate isomerase and transketolase activities were decreased; in contrast with this transaldolase activity did not change significantly. Hypophysectomy caused a 50% fall in transketolase activity that was partially reversed by treatment with thyroxine and almost fully reversed by treatment with growth hormone for 8 days. 5. The results are discussed in relation to the hormonal control of the non-oxidative reactions of the pentose phosphate cycle, the marked changes in transketolase activity being particularly outstanding.
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PMID:The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver. 579 34

1. Measurements were made of the activities of the enzymes of the pentose phosphate pathway concerned in both the oxidative (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) and the non-oxidative (ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase, transketolase and transaldolase) reactions of this pathway, together with hexokinase and phosphoglucose isomerase, in adipose tissue in a variety of nutritional and hormonal conditions. 2. Starvation for 2 days caused a significant decrease in the activities of all the enzymes of the pentose phosphate pathway, with the exception of glucose 6-phosphate dehydrogenase, when expressed as activity/2 fat-pads; only the activities of ribose 5-phosphate isomerase and ribulose 5-phosphate epimerase were significantly decreased on the basis of activity/mg. of protein. Re-feeding with a high-carbohydrate or high-fat diet for 3 days restored the activity of all the enzymes of the pentose phosphate pathway to the range of the control values, with the exception of transketolase, which showed a marked ;overshoot' in rats re-fed with carbohydrate. Starvation for 3 days caused a marked decrease in the activities of glucose 6-phosphate dehydrogenase and transketolase. 3. On the basis of activity/two fat-pads, alloxan-diabetes caused a marked decrease, to about half the control value, in the activities of all the enzymes concerned in the pentose phosphate pathway, transketolase showing the smallest decrease; hexokinase and phosphoglucose isomerase activities were also decreased. Treatment with insulin for 3 and 7 days raised the activities to normal or supranormal values, transketolase showing the most marked ;overshoot' effect. On the basis of activity/mg. of protein the activity of none of the enzymes was significantly decreased in alloxan-diabetes; transketolase and transaldolase activities were raised above the control values. With insulin treatment for 3 or 7 days the activities of all the enzymes were significantly increased, except that of ribulose 5-phosphate epimerase at the shorter time-interval. Glucagon treatment did not alter any of the enzyme activities expressed on either basis. 4. Thyroidectomy caused a decrease of 30-40% in the activities of enzymes of the pentose phosphate pathway, except for transketolase activity, which fell to 50% of the control value. Little change occurred in adipose-tissue weight or protein content. 5. Adrenalectomy caused a decrease of 40% in the activity of glucose 6-phosphate dehydrogenase and of 20-30% in the activities of the remaining enzymes of the pentose phosphate pathway; hexokinase activity was also decreased. Treatment with cortisone for 3 days did not significantly raise the activity from that found in adrenalectomized rats. Treatment of normal rats with high doses of cortisone had no significant effect on the activities of the enzymes of the pentose phosphate pathway in adipose tissue. 6. The changes in enzyme activities are discussed in relation to: (a) the concept of constant-proportion groups of enzymes; (b) the known changes in the flux of glucose through alternative metabolic pathways; (c) the pattern of change found in liver with similar hormonal and dietary conditions.
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PMID:The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative nd non-oxidative reactions and related enzymes of the cycle in adipose tissue. 581 81


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