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

The relationship between glucose oxidation and glycolysis was examined in tumoral pancreatic islet cells with either rapid or decreased cell growth. In the control RINm5F cells, the utilization of D-[5-3H]glucose progressively augmented at increasing concentrations of D-glucose (0.2 to 16.7 mM), whereas D-[6-14C]glucose oxidation reached its maximal value at about 3.0 mM D-glucose. The 14CO2/3HOH ratio progressively decreased at increasing hexose concentrations, being about 5-times higher at 0.2 than 10.0-16.7 mM. These experiments were repeated in cells cultured in the presence of D,L-alpha-difluoromethylornithine, which inhibits RINm5F cell proliferation. At 0.2 mM D-glucose, 14CO2 output was severely decreased but 3HOH production little affected, resulting in a marked fall of the 14CO2/3HOH ratio. On the contrary, at 16.7 mM D-glucose, 3HOH formation was more markedly decreased than 14CO2 output, resulting in an increased 14CO2/3HOH ratio. These findings provide a model for the interference of cell growth with D-glucose metabolism in islet cells. Rapid growth causes a preferential stimulation of the Krebs cycle relative to glycolysis at a low glucose concentration, whilst increasing glycolysis more than oxidation at high concentrations of the hexose.
Diabetes Res 1991 Jun
PMID:Relationship between D-glucose oxidation and glycolysis in tumoral pancreatic islet cells with either rapid or decreased cell growth. 181 13

Several studies in the last decade have highlighted the importance of the hexose sugars and especially glucose, as being responsible for alterations to living protein and other molecules. The phenomenon of nonenzymatic glycation--by which the carbonyl group of glucose can directly condense with a free amino group--may be relevant for the process of aging and for the pathogenesis of late diabetic complications. Thus life-long exposure to normoglycemia in non diabetic subjects or a shorter exposure but continued association with a hyperglycemic milieu, as in diabetes mellitus, have both been shown to lead to the formation and accumulation of irreversible and highly reactive advanced glycation endproducts (AGE) over long-lived, fundamental molecules such as the constituents of arterial wall collagen, basement membranes, nerve myelin, DNA and others. For example, the introduction of foreign AGE groups into proteins might alter their tertiary structure and therefore modify their function or activity. By increasing protein-to-protein cross-links AGE could reduce protein turnover, with consequential increases in levels of modified and thus less reactive molecules. Moreover, AGE could initiate an immune response with the production of specific antibodies. Reducing the extent of nonenzymatic glycation could effectively reduce the accumulation of AGE. Many authors are experimenting with methods to achieve this aim. Amongst the products tested are aspirin and aminoguanidine which compete with glucose for the same protein amino group. D-lysine is also being investigated on the principle that by reacting with glucose in circulation, it could effectively prevent it from reaching the amino group on the protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 Jan
PMID:Advanced nonenzymatic glycation endproducts (AGE): their relevance to aging and the pathogenesis of late diabetic complications. 181 91

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

Adult rats injected with streptozotocin during the neonatal period displayed in the fed state moderate hyperglycemia. However, the percentages of glycated hemoglobin in erythrocytes and glycated lactate dehydrogenase in liver and pancreatic islets, as well as the sorbitol and glycogen content of the islets, were not significantly increased. Likewise, in intact islets, the ouabain-sensitive inflow of 86Rb+, and the ratio between 3H2O production from D-[2-3H]glucose and D-[5-3H]glucose were not different in control and streptozotocin-injected rats. These findings suggest that the alteration in both the mitochondrial catabolism of D-glucose and secretory response to the hexose previously documented in the islets of the latter animals are not attributable to factors such as the excessive nonenzymatic glycation of cytosolic proteins, sorbitol or glycogen accumulation, or impaired Na+, K(+)-adenosine triphosphatase (ATPase) activity. Although a contributive role of glucotoxicity in the impaired function of beta cell in this model of non-insulin-dependent diabetes should not be ruled out, it is speculated that streptozotocin might also cause a long-term damage of key mitochondrial dehydrogenases in the pancreatic beta cells and, possibly, their precursor cells.
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PMID:Neonatal streptozotocin injection: a model of glucotoxicity? 183 15

Cultured neuroblastoma, cerebral microvessel endothelial, and retinoblastoma cells were used to examine the mechanism of acute inhibition by D-glucose of myo-inositol uptake. Acute exposure of the cells to 30 mM D-glucose caused a significant decrease in Na(+)-dependent myo-inositol uptake in all three cell types. The effect of D-glucose to acutely inhibit myo-inositol uptake was dependent on the extracellular glucose concentration and was not reversed by sorbinil. 2-Deoxy-D-glucose (30 mM), 3-O-methyl-D-glucose (30 mM), and cytochalasin B (100 microM) did not acutely inhibit myo-inositol uptake. These data suggest that the hydroxyl groups on carbons 2 and 3 of D-glucose, which in a Haworth projection appear trans to each other, are important for inhibitory activity. Other monosaccharides (30 mM) having a similar 2,3-trans-diol configuration, L-glucose, D- and L-fucose, D- and L-galactose, D- and L-xylose, and D-arabinose, all to varying degrees significantly inhibited myo-inositol uptake. In all cases, the L-isomers were more potent inhibitors of myo-inositol uptake than the corresponding D-isomers. Monosaccharides (30 mM) having hydroxyl groups on carbons 2 and 3 in a cis configuration, D-mannose, L-rhamnose, D-allose, and D-ribose, did not acutely inhibit myo-inositol uptake. Replacing the hydroxyl group with a fluorine on carbons 2 or 3 of D-glucose negated its inhibitory activity of myo-inositol uptake. In contrast, replacing the hydroxyl group with a fluorine on carbon 6 of D-glucose did not block its inhibition of myo-inositol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Aug
PMID:Trans-hydroxyl group configuration on carbons 2 and 3 of glucose. Responsible for acute inhibition of myo-inositol transport? 186 May 53

In 1930 adenosine triphosphate appeared in the literature from W. A. Engelhardt's work on avian erythrocytes. This was an early example of oxidative phosphorylation in intact cells, and it required methylene blue and oxygen. Both Belitser and I realized that the use of Warburg manometers for aeration was critical in order to generate oxidative phosphorylation of glucose in tissue preparations. Test tube techniques did not work. In 1956 we were able to describe a human type of diabetes called "galactose diabetes," in which consumption of human or cows' milk provokes mental retardation. Replacement of human or cows' milk products with "vegetable milk" formula in early infancy can prevent retardation. We determined that the disease results from a defect of galactose-one-phosphate uridylyl-transferase, a hereditary enzyme. This type of enzyme defect, if discovered and treated in early infancy, is a benign molecular disease. Regulation of transport systems in mammalian cell cultures are frequently complex energized systems. Perhaps my greatest surprise in this regard was the mere fact that an all-cis "odd" hexose-D-allose turned out to be a highly intense down-regulator of the hexose transport system. Additions of inhibitors of oxidative phosphorylation (such as oligomycin or di-nitrophenol) arrested the allose-mediated down-regulation. We have reason to suspect that the strong down-regulator is a phosphorylated form of D-allose. Thus ends my story about oxidative energized biological phosphorylation systems.
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PMID:50 years of biological research--from oxidative phosphorylation to energy requiring transport regulation. 188 94

The kinetic characteristics of 3-O-methyl glucose (3-OMG) uptake were examined in red blood cells (RBC) from seven normal individuals (controls) and nine patients with non-insulin-dependent diabetes mellitus (NIDDM) treated with diet and oral hypoglycemic medication. Comparison of rates of 3-OMG uptake at 5 different substrate concentrations revealed significantly higher overall 3-OMG uptake in the diabetic group (P less than 0.0001). Kinetic parameters obtained for individual subjects showed there was not a significant difference in the Km between the diabetic (3.17 +/- 0.45 mM; mean +/- SE) and the control (2.46 +/- 0.25 mM) groups. However, Vmax was significantly increased (61%; P less than 0.025) in the diabetics (217.8 +/- 28.9 pmol/2 sec per 10(6) cells) compared to controls (135.2 +/- 15.6 pmol/2 sec per 10(6) cells). There was no correlation between HbA1C levels in the diabetic patients and Vmax values for 3-OMG uptake, suggesting that the increased hexose uptake was not accounted for simply by increased glycosylation in these cells. Glucose transport in RBC in hyperglycemic states may be a useful model for delineating the regulation of the non-insulin-mediated disposal of glucose in diabetes.
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PMID:Non-insulin dependent diabetic patients have increased glucose uptake in red blood cells. 204 61

1. The effects of streptozotocin-induced diabetes mellitus on active jejunal glucose uptake in vivo, and on galactose movement across the brush-border (phlorhizin-sensitive) and basolateral (phlorhizin-insensitive) membranes of isolated upper and mid-villus enterocytes has been studied. 2. Chronic diabetes increased unidirectional phlorhizin-sensitive galactose uptake by mid-villus but not upper villus cells. In contrast, phlorhizin-insensitive uptake by both cell populations was enhanced by diabetes. 3. Diabetes increased glucose absorption in vivo by mechanisms which were unrelated to hyperphagia. Mucosal hyperplasia acting together with an epithelium containing a higher proportion of mature enterocytes is the most likely explanation for the response. 4. We conclude that, during diabetes, the mid-villus region is an important site of adaptation with functional changes occurring at both the brush-border and basolateral membranes. The increased hexose transport ability of the basolateral membrane is retained during cell transit along the villus.
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PMID:Diabetes mellitus and sugar transport across the brush-border and basolateral membranes of rat jejunal enterocytes. 214 23

In epithelial cells isolated from rat small intestine and incubated in the presence of 1 mM glucose, streptozotocin-induced diabetes reduced, by 46 and 29%, respectively, the rates of both glucose utilization and L-lactate formation. These effects were accompanied by a significant decrease of enterocyte fructose 2,6-bisphosphate concentration (about 50%) and of the glycolytic flux through the reaction catalyzed by 6-phosphofructo 1-kinase. The diminution of enterocyte fructose 2,6-bisphosphate levels caused by diabetes occurred in spite of an increase of hexose 6-phosphate concentration, and was associated with a reduction in the amount of active form of 6-phosphofructo 2-kinase; total activity of this enzyme was not significantly modified. Diabetes also caused an acceleration in the rate of 3-O-methyl-D-(14C) glucose uptake and increased hexokinase activity in enterocytes. Lactate dehydrogenase, pyruvate kinase and 6-phosphofructo 1-kinase activities were not found to be significantly different in epithelial cells isolated from control or diabetic animals. Our results indicate that a reduction of the glycolytic flux in enterocytes could collaborate to increase intestinal glucose absorption in the diabetic state.
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PMID:Effect of streptozotocin diabetes on the glycolytic flux and on fructose 2,6-bisphosphate levels in isolated rat enterocytes. 216 51


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