Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There have been differences of opinion among authors concening in the levels of red cell 2,3-diphosphoglycerate (2,3-DPG) and nucleotides in nonacidotic diabetic patients. Our data suggest that abnormal levels of 2, 3-DPG in diabetic patients are related to the presence of vascular complications and not to the duration of the disease per sec. 2,3-DPG levels are normal in diabetic patients with no evidence of vascular complications (group A). In ambulatory patients with vascular complications (group B), significantly higher levels of 2,3-DPG are found than in normal subjects and patients in group A. In hospitalized diabetic patients with active peripheral vascular complications (group C), levels of 2,3-DPG are likewise significantly increased over those of normal subjects and patients of group A. 2,3-DPG was found to be significantly elevated in patients of group C as compared with group B. 2,3-DPG levels in venous blood from infected legs as compared with those of the peripheral venous blood were not significantly different, thereby ruling out local factors. There were no differences in the blood lactate levels in any of the group studied. The elevation of the 2,3-DPG levels may be a reflection of attempted red blood cell compensation for tissue hypoxia in the diabetic with vascular disease.
Diabetes 1975 Aug
PMID:Red cell 2, 3-diphosphoglycerate levels among diabetic patents with and without vascular complications. 115 35

Maternal tissue oxygenation was reflected by the level of red cell, 2,3-diphosphoglycerate (DPG) was measured before, during and after normal pregnancy. Following an initial fall at the beginning of pregnancy there was a significant rise in the mean level of DPG during pregnancy with an abrupt fall in the puerperium. The mean red cell DPG level in the third trimester of pregnancies complicated by pre-eclampsia and diabetes was not statistically different from the normal but the mean value of all pregnancies in which the fetus was stillborn or growth retarded was significantly lower (p less than 0-001). The possible mechanism of the changes in normal and abnormal pregnancy is discussed and it is suggested that the measurement of red cell DPG in the third trimester of pregnancy may prove to be a useful parameter of placental oxygenation.
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PMID:Tissue oxygenation and red cell 2,3-diphsophoglycerate in normal and abnormal pregnancy. 126 47

Hematologic values are compared for normal and streptozotocin-induced diabetic rats after 6 weeks of induced diabetes. Most hematologic parameters were the same in the two groups except for blood glucose, glycated hemoglobin, and 2,3 diphosphoglycerate, all of which were elevated in the streptozotocin group. However the P50 (the PO2 at which the oxygen-carrying capacity of blood is 50% of maximal) remained normal. We hypothesize that a left shift in the oxyhemoglobin dissociation curve caused by the glycation of a small percentage of the hemoglobin is compensated by elevation in the 2,3-diphosphoglycerate which returns the P50 to normal values. This compensatory mechanism also occurs in some stages of human diabetes.
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PMID:Comparison of hematologic parameters in normal and streptozotocin-induced diabetic rats. 131 51

Peripheral neuropathy remains a major complication of diabetes. Numerous etiological theories of metabolic and/or vascular disturbances have been suggested including decreased endoneurial oxygen tension with presumed tissue hypoxia. Increases in the affinity of hemoglobin for oxygen (Hb-O2 affinity) may also produce tissue hypoxia and such Hb-O2 affinity changes have been implicated in the pathogenesis of diabetic microangiopathy. In order to test whether affinity hypoxia might contribute to the development of diabetic peripheral neuropathy, we have utilized a rat model of high and normal Hb-O2 affinity produced by backcrossing animals with increased and decreased levels of 2,3-diphosphoglycerate (DPG). Diabetes was induced in ten high and ten low DPG animals with a tail vein injection of 55 mg/kg streptozotocin (STZ). Five animals in each group were treated with 2.4 U protamine zinc insulin (PZI)/day while the remaining animals were untreated. All rats were killed after 30 days, sections of tibial and sural nerve were rapidly removed and processed for teased fiber analysis. A minimum of 125 axons were assessed per nerve for E degeneration (myelin ovoids) using the classification developed by Dyck et al. Untreated animals, regardless of DPG levels, demonstrated 0% neuropathy. In contrast, all insulin-treated animals showed degeneration (0.4-17%) that inversely correlated with the DPG level (r = -0.59, P less than 0.04). The results of this study suggest that the level of RBC DPG (and presumably the Hb-O2 affinity) with its attendant effect on tissue oxygen release may play a role in the development of peripheral neuropathy in STZ-induced diabetic rats treated with insulin.
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PMID:Oxygen affinity of hemoglobin and peripheral nerve degeneration in experimental diabetes. 203 5

A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb Hope, beta 136(H14)Gly----Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H+ (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb Hope is also described.
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PMID:Hb Hope, beta 136(H14)Gly----Asp, in a diabetic Japanese female and its functional characterization. 270 63

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.
Diabetes 1989 Jul
PMID:Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus. 273 64

2,3-Bisphosphoglycerate, glucose 1,6-P2 and fructose 2,6-P2 have been recognized as regulatory signals implicated in the control of metabolism, oxygen affinity of red cells and other cellular functions. The alterations of their metabolism constitute a novel area in molecular pathology. The concentration of 2,3-bisphosphoglycerate in erythrocytes changes in a number of pathological conditions. An inherited deficiency of the multifunctional enzyme involved in the synthesis and breakdown of 2,3-bisphosphoglycerate in erythrocytes has been reported. The levels of glucose 1,6-P2 are reduced in the liver and in the muscle of rats with experimentally induced diabetes. In muscle of genetically dystrophic mice a decrease in the levels of glucose 1,6-P2 has been found, probably resulting from enhancement of glucose 1,6-P2 phosphatase activity. Fructose 2,6-P2 levels are decreased in the liver of experimental diabetic mice and rats, and elevated in the liver of genetically obese animals.
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PMID:Bisphosphorylated metabolites of glycerate, glucose, and fructose: functions, metabolism and molecular pathology. 355 87

Human aorta, brain, and muscle aldose reductase, partially purified by DEAE-cellulose (DE-52) column chromatography, is activated 2-2.5-fold on incubation with 10 microM each of glucose-6-phosphate, NADPH, and glucose for 20 min at 25 degrees C. The activation of the enzyme was established by following the NADPH oxidation as well as the sorbitol formation using glucose as substrate. The activated form of aldose reductase exhibited monophasic kinetics with glucose and glyceraldehyde, whereas the unactivated or native enzyme exhibited a biphasic kinetics with both the substrates. The activated enzyme was less susceptible to inhibition by aldose reductase inhibitors such as sorbinil, alrestatin, and quercetrin as compared with the unactivated enzyme. Similarly, the native enzyme was strongly inhibited by some of the phosphorylated intermediates of glycolytic pathway, such as 3-phosphoglycerate, 1,3-diphosphoglycerate, 2,3-diphosphoglycerate, and ADP, whereas the activated enzyme was either not inhibited or inhibition was 20-30% only. Partially purified aldose reductase from the normal human lens exhibited properties similar to the native enzyme of other tissues, whereas the enzyme from clear lens obtained from diabetic subjects with severe hyperglycemia expressed properties similar to the in vitro activated enzyme of aorta, brain, and muscle.
Diabetes 1985 Nov
PMID:Activation of aldose reductase from human tissues. 393 Mar 26

Thirty-three diabetic subjects were given the aldose reductase inhibitor sorbinil (Pfizer, UK) for 3 wk. There was a significant fall in mean erythrocyte sorbitol concentration over this period. In all subjects erythrocyte sorbitol concentrations after treatment were within or below the range found in normal subjects. No changes in erythrocyte 2,3-diphosphoglycerate (2,3-DPG) or myo-inositol concentrations, plasma beta-thromboglobulin (beta-TG) concentration, or P50--a measure of the oxygen affinity of hemoglobin--were observed. There was a high incidence of adverse reactions to the drug.
Diabetes Care
PMID:Effects of sorbinil treatment on erythrocytes and platelets of persons with diabetes. 394 46

Erythrocyte 2,3-diphosphoglycerate and haemoglobin A1c concentrations were measured in 26 clinically normoxic patients with type 1 (insulin dependent) diabetes mellitus. The concentration of 2,3-diphosphoglycerate theoretically required to maintain normal erythrocyte oxygen delivery function in each subject was calculated and compared with the measured concentrations. In the majority of diabetic patients 2,3-diphosphoglycerate concentrations were sufficient to keep the erythrocyte oxygen dissociation curve within the normal range under otherwise normal blood conditions. There was, however, a minority of patients in which this was not true. It is concluded that the increased erythrocyte 2,3-diphosphoglycerate concentrations in clinically normoxic diabetic subjects are generally less than compensatory for the effect of haemoglobin A1c formation on the haemoglobin-oxygen dissociation curve.
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PMID:Borderline maintenance of erythrocyte 2,3-diphosphoglycerate concentrations in normoxic type 1 (insulin dependent) diabetic subjects. 395 4


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