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)

The effect of type I (insulin-dependent) diabetes mellitus on the key glycolytic enzymes of red cells was studied. The activities of hexokinase, phosphofructokinase and pyruvate kinase were found to be significantly (p less than 0.01) increased in diabetic patients. Treatment with insulin restored the enzyme activities to normal. The increased activities of the key enzymes may help to regulate red cell ATP level in response to the elevated Na:K pump rate in diabetes. The increased activities of these enzymes may also be due to a greater proportion of young erythrocytes in diabetic patients because of a shortened red cell life span as compared to normal.
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PMID:Effect of type I (insulin-dependent) diabetes mellitus on key glycolytic enzymes of red blood cells. 253 57

The activity and kinetics of phosphofructokinase were measured in the postmicrosomal supernatant of livers removed from either normal or streptozotocin-induced diabetic rats. The activity of the enzyme was lower in diabetic than normal rats. However, the relative magnitude of changes in reaction velocity evoked by different concentrations of D-fructose 6-phosphate, ATP, D-glucose 1,6-bisphosphate and/or D-fructose 2,6-bisphosphate were comparable in normal and diabetic rats. Such was also the case after separation of cytosolic proteins from low molecular weight metabolites by gel filtration chromatography. These findings suggest that a sustained increase in intracellular D-glucose concentration, as presumably occurring in hepatocytes of diabetic animals, does not result in any obvious alteration of the intrinsic kinetic properties of phosphofructokinase.
Diabetes Res 1989 Nov
PMID:Activity and kinetics of liver 6-phosphofructokinase in normal and diabetic rats. 253 26

The effects of a beta-blocker, propranolol, on the enzyme and isoenzyme activities in the heart muscle in vitro and concomitant histopathology of the component cells of the islets of Langerhans were studied in the Wistar rats after treatment with streptozotocin and isoproterenol. The biochemical data indicated that the isoproterenol induced myocardial infarction (MI) precipitates an acute diabetic response in the rat heart. The superimposition of MI in diabetes mellitus caused significant inhibition of phosphofructokinase and hexokinase in the heart muscle. The lactate dehydrogenase depicted shifting of H-type to M-type in diabetes with or without MI. The drugs, when administered in combination, brought distinctive histopathological changes in beta-cells of the pancreatic islets including degranulation, hyalinosis and a near-total destruction; however A and D cells remained more or less unaffected. The effect of propranolol in diabetes mellitus was uncertain but in MI with or without prior diabetes, the drug inversely altered the activities of all the cardiac enzymes, besides stimulating a mild recuperation of the cells of the endocrine parenchyma.
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PMID:Myocardial dysfunction in diabetic rats: influence of beta-adrenoceptor blockade (propranolol). 263 86

The aim of this study was to investigate the metabolic effects of short-term fasting in obese diabetic patients and to correlate the observed changes with the activity of hepatic key enzymes in an animal model of obesity-associated diabetes (ob/ob mice, C57BL/6J strain). In obese diabetic patients (ODP), a 72-h fast (causing slight change in body weight) decreased fasting glycemia by 3.82 +/- 0.79 mmoles/l and significantly improved glucose tolerance (OGTT) while reducing basal and stimulated insulinemia, whereas in obese non-diabetic patients (ONDP) only a small decrease in fasting glycemia (1.24 +/- 0.51 mmoles/l) occurred. This suggests that in ODP hyperphagia is a factor contributing to maintain hyperglycaemia and glucose intolerance (in the face of hyperinsulinaemia, indicating insulin resistance). In fed obese hyperglycaemic mice (OHM), which are a good model of the human obesity-associated diabetes, hepatic fructose-1,6-diphosphatase (F16Pase) and glucose-6-phosphatase (G6Pase), involved in glucose production, showed increased activity (+52 and +200 per cent, respectively) compared to control mice (CM), and the ratios of F16Pase and G6Pase to the opposing enzymes phosphofructokinase (PFK1) and glucokinase (GK), i.e. the F16Pase/PFK1 and G6Pase/GK ratios, were increased by 38 and 101 per cent, respectively, suggesting increase in gluconeogenesis and perhaps in glycogenolysis. In the 48-h fasted OHM, F16Pase activity was decreased (-30 per cent) compared to the fed animals, while the activity of G6Pase showed a smaller and statistically not significant change (-22 per cent). In contrast, in the CM a 48-h fasting was associated with a trend toward increased F16Pase (+22 per cent) and G6Pase (+173 per cent). However, since PFK1 and GK decreased to a similar extent in OHM and CM, the F16Pase/PFK1 and G6Pase/GK ratios, basally elevated in the OHM, did not change with fasting, whereas in the CM they showed a striking elevation (+71 and +274 per cent, respectively). The basally elevated F16Pase/PFK1 and G6Pase/GK ratios (functionally linked to glucose production) in the OHM may contribute to maintain hyperglycaemia; in these mice, the lack of further increase in the glucose production-related F16Pase/PFK1 and G6Pase/GK ratios (which occurs in CM) with fasting might allow that the interruption of the afflux of dietary carbohydrates ameliorates the glycaemic level. Similar mechanisms might occur also in the ODP.
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PMID:Metabolic effects of short-term fasting in obese hyperglycaemic humans and mice. 283 Nov 63

In rat pancreatic islets, hypoxia severely decreased both the oxidation of D-[U-14C]glucose and the release of insulin evoked by D-glucose. The production of [14C]lactate was increased in the hypoxic islets, the relative magnitude of such an increment being greater at low (2.8 mM) than high (8.3 and 16.7 mM) D-glucose concentrations. Hypoxia increased the detritiation of D-[5-3H]glucose at low glucose concentration (2.8 mM), failed to affect 3H2O production at an intermediate glucose level (8.3 mM), and inhibited the utilization of D-[5-3H]glucose at a higher hexose concentration (16.7 mM). In tumoral islet cells (RINm5F line) exposed to 16.7 mM D-glucose, hypoxia decreased D-[U-14C]glucose oxidation to the same extent as in normal islet cells, but increased the production of [14C]lactate and 3H2O to a greater extent than in normal islets. These findings indicate that the Pasteur effect is operative in islet cells. The experimental data also suggest that, under normal conditions of oxygenation, high concentrations of D-glucose lead to both activation of phosphofructokinase and stimulation of mitochondrial oxidative events in normal, but not tumoral, islet cells.
Diabetes Res 1988 Feb
PMID:Hexose metabolism in pancreatic islets: the Pasteur effect. 284 Feb 31

Muscle homogenates representing slow-twitch oxidative, fast-twitch oxidative-glycolytic, fast-twitch glycolytic, and mixed fiber types were prepared from normal, diabetic, and insulin-treated diabetic rats. Diabetes was induced by injection of 80 mg . kg-1 of streptozotocin. The activities of citrate synthase, succinate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase were employed as markers of oxidative potential, whereas phosphorylase, hexokinase, and phosphofructokinase activities were used as an indication of glycolytic capacity. Diabetes was associated with a general decrement in the activity of oxidative marker enzymes for all fiber types except the fast-twitch glycolytic fiber. In contrast, the fast-twitch glycolytic fibers demonstrated the greatest decline in glycolytic enzymatic activity. Insulin-treated animals, either trained or untrained, exhibited enzyme activities similar to their normal counterparts. Exercise training of diabetic rats mimicked the effect of insulin treatment and caused a near normalization of the activity of the marker enzymes. These findings suggest that the enzymatic potential of all skeletal muscle fiber types of diabetic rats may be normalized by exercise training even in the absence of significant amounts of insulin.
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PMID:Influence of training on skeletal muscle enzymatic adaptations in normal and diabetic rats. 293 94

Sera from cancer patients specifically suppressed phosphofructokinase (fructose-6-phosphate kinase [PFK], EC 2.7.1.11), a rate-limiting enzyme in the glycolysis pathway. Among 418 cancerous sera, 68.7% evidence suppression; there was no organ specificity. Among 42 sera from early gastric cancer patients, 29 (69.0%) were positive, as were advanced gastric cancer, 14/19 (73.3%) pancreas cancer, and 75/101 (74.3%) lung cancer sera. In contrast 6/50 (12.0%) sera from patients with gastroduodenal ulcer, 3/23 (13.0%) with myoma uteri, and 0/6 with lung tuberculosis were positive. Patients with diabetes mellitus and those receiving steroid hormone therapy showed strong positive suppression. Comparative studies using other tumor markers (immunosuppressive acid protein, carcinoembryonic antigen, alpha-fetoprotein, beta 2-microglobulin, and ferritin) and the same sera used from PFK assay showed that the PFK method was two to three times more sensitive. Sephadex G-200 column chromatography revealed that the PFK-suppressive activity was retained in the postalbumin fraction. The PFK method may represent a promising new cancer screening method.
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PMID:A new cancer marker: a possible cancer screening method based on the suppression of phosphofructokinase by sera from cancer patients. 293 46

Hearts isolated from non-insulin-dependent diabetic rats were found to exhibit reduced rates of basal and insulin-stimulated glucose metabolism. Since tissue levels of fructose 1,6-bisphosphate are significantly reduced in the diabetic heart, it was concluded that phosphofructokinase may be inhibited. However, neither glycogen nor glucose 6-phosphate accumulated in the myocyte, indicating that the phosphofructokinase reaction was not a bottleneck diverting substrate away from glycolysis. The other major factor contributing to decreased glycolytic flux in the diabetic heart is the impairment in glucose transport. Both basal and insulin-stimulated transport of 3-O-methyl-D-glucose was 30% less in the diabetic heart. While insulin sensitivity was unaltered in the diabetic rat, insulin responsiveness was decreased, indicating that the impairment in insulin-stimulated hexose transport was caused by a post-receptor defect. The net result of these abnormalities in glucose metabolism is a significant reduction in the rate of ATP synthesis by the diabetic heart.
Diabetes 1986 May
PMID:Postreceptor myocardial metabolic defect in a rat model of non-insulin-dependent diabetes mellitus. 293 76

In contrast to liver, adipose tissue, and muscle, in which the diabetic state is associated with a "catabolic response," some tissues, typically the kidney and perhaps the intestinal mucosa and some vascular cell types, show an "anabolic response" to diabetes, with enhanced activity of the anabolic pathways and diminished activity of the catabolic ones. The kidney of alloxan or streptozotocin diabetic rats is hypertrophied, and shows enrichment in intracellular glycogen and abundant accumulation of glycoprotein material at the basement membrane level. Accordingly, protein synthesis and the enzymes of glucose utilization as well as those engaged in UDP sugar formation or in the hydroxylation and glycosylation processes (required for glycoprotein synthesis) show increased activity in the diabetic kidney, while the catabolic, lysosomal enzymes (cathepsin D and several glycosidases) are depressed. We observed a reduction of -24% in the activity of cathepsin D and -23% in that of galactosidase in the kidney of streptozotocin diabetic mice, as opposed to increases of +135 and +32%, respectively, found in liver. It is not known which factor(s) may be responsible for such an anabolic response of some tissues to diabetes, but persistent hyperglycemia and/or some hormonal abnormalities may be involved. The above data refer to changes in tissue enzyme content caused by induction-repression mechanisms, but rapid (activation-inhibition) effects may also occur. We observed that preincubation of slices of mouse kidney cortex for 10 min with 20.8 mmole/liter glucose resulted in a 80% activation of phosphofructokinase, as assayed in the tissue homogenate at physiological (50 mumole/liter) concentration of the substrate fructose-6-P, suggesting that hyperglycemia may be responsible for some of the metabolic changes occurring in the diabetic kidney.
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PMID:Anabolic response of some tissues to diabetes. 293 59

Seven cytoplasmic enzyme activities were measured in extracts of mononuclear leukocytes (lymphocytes plus monocytes) obtained from 19 type II diabetic humans and 10 healthy control subjects. 6-Phosphofructokinase activity was significantly decreased in cell extracts from diabetics, while other enzyme activities were similar in diabetics and controls. Since the effects of starvation on enzyme activities are sometimes similar to the effects of diabetes, the studies were repeated in 5 control subjects after a 2-day fast. This short period of starvation did not mimic the effect of diabetes on 6-phosphofructokinase activity. The decreased enzyme activity was not correlated with percent specific insulin binding to monocytes in the same cell preparations nor to clinical variables such as obesity or the broad range of fasting plasma glucose values encountered among the diabetics. We conclude that 6-phosphofructokinase activity in mononuclear leukocytes, as in other tissues, may be a marker for a postreceptor lesion associated with the insulin resistance found in type II diabetes mellitus.
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PMID:Impaired 6-phosphofructokinase activity in mononuclear leukocytes from patients with type II diabetes mellitus. 295 96


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