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)

Rat islets contain the acid-labile activator of phosphofructokinase, fructose-2,6-bisphosphate. The islet content in activator is higher in islets exposed to glucose (16.7 mM) than in islets deprived of glucose. The islets display fructose-6-phosphate, 2-kinase activity with a Km for fructose-6-phosphate close to 0.08 mM. Glucose fails to affect the activity of this enzyme. It is proposed that the effect of glucose to increase the islet content of fructose-2,6-bisphosphate is attributable, in part at least, to the glucose-induced increase in the concentration of fructose-6-phosphate in the islet cells.
Diabetes 1982 Jan
PMID:Glucose-induced accumulation of fructose-2,6-bisphosphate in pancreatic islets. 621

The phosphofructokinase stabilizing factor, believed to be a peptide of molecular weight 3,800 (Dunaway G.A. and Segal H.L., 1976, J. Biol. Chem. 251, 2323-2329), shares many chemical and biological properties with fructose 2,6-bisphosphate. It co-migrated with it upon gel filtration in the molecular weight range 300-400 or 3,000-4,000 depending upon the ionic strength of the solution. Fructose 2,6-bisphosphate is the most potent phosphofructokinase stabilizing agent present in the liver of a fed rat. Its disappearance during fasting and diabetes could account for the faster rate of degradation of phosphofructokinase reported to occur under these conditions. The effect of starvation to decrease by 60% the phosphofructokinase content of the liver is, however, for its greatest part, related to a non-specific decrease in liver mass.
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PMID:The role of fructose 2,6-bisphosphate in the long-term control of phosphofructokinase in rat liver. 622 34

The three important key-enzymes HK, PFK, PK may be influenced by insulin. We have, therefore, measured these enzyme activities in the erythrocytes in a total of 119 childrens suffering from juvenile diabetes type I, 44 of them with a good state of metabolic control and 75 with a bad control. In both groups the activities of the three enzymes were not significantly different. Compared with the reference values, PFK and PK, were mild diminished, HK slowly elevated in both groups of diabetics. We don't find remarkable changes which could be responsible for a shortened red cell life span. The mechanism of hemolysis in diabetics is probably caused by oxidant damage to the membrane.
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PMID:[Erythrocyte metabolism in type I diabetes mellitus (key enzymes of glycolysis)]. 623 16

Changes in the profile of two glycolytic enzymes, phosphofructokinase and pyruvate kinase, in different regions of rat brain were studied under alloxan-induced diabetes. A regional variation of the effect of diabetes on brain was noted - the cerebral hemispheres and cerebellum showed decreased activity of the enzymes, while the brain stem remained relatively unaffected. The changes in enzyme activities in the brain regions were more pronounced at the early days of diabetes, particularly at 8 days. Insulin administration to the diabetic animals restored the activity of the enzymes. The results indicate a regionally variable effect of diabetes on the two key glycolytic enzymes, and bring out a role of insulin in the regulation of brain glycolysis.
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PMID:Changes in phosphofructokinase and pyruvate kinase in rat brain regions during alloxan-induced diabetes. 623 20

A newly developed specific radioimmunoassay was used to quantify phosphofructokinase protein directly and independently of assayable activity in liver and kidney cytosol of normal fed, starved and alloxan-diabetic rats. In the fed state, liver phosphofructokinase concentration was 0.096 microM and the kidney enzyme was 0.086 microM (mumol/kg of tissue). In the starved state (24h), liver and kidney phosphofructokinase concentrations decreased by 30%. Prolonged starvation up to 72h did not further decrease enzyme concentration. In liver, total enzyme content during starvation declined by more than 50%, secondary also to a decrease in liver weight. In the alloxan-diabetic rats, there was a 22% decrease in enzyme protein concentration in liver and kidney. Total enzyme content per liver actually decreased much more (46%), because diabetes also resulted in a decrease in liver size. In conjunction with assayable activity measurements, the results of the radioimmunoassay allowed us to calculate the apparent specific activity of the enzyme. The specific activity of the kidney enzyme was 2-3 times that of the liver. Little or no change in specific activity of the liver or kidney enzyme occurred as a result of starvation or chemically induced diabetes. Tissue enzyme concentrations of phosphofructokinase unequivocally reconcile the ultimate results of changing rates of synthesis and degradation and are useful data in the design of spectrophotometric, kinetic, aggregation-disaggregation and other studies.
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PMID:Quantification of liver and kidney phosphofructokinase by radioimmunoassay in fed, starved and alloxan-diabetic rats. 624 Feb 62

Streptozotocin-induced maternal diabetes has been shown to alter developmental patterns of carbohydrate-metabolizing enzyme activities, glycogen deposition and surfactant levels in late fetal rat lung in a tissue-specific manner, as follows: (a) marked reduction in glycogen synthase a activity, due to aberrant interconversion between active and inactive forms of the enzyme; less glycogen was thus accumulated; (b) lowered activities of hexokinase, phosphofructokinase and pyruvate kinase at term; (c) reduced disaturated phosphatidylcholine (surfactant) concentrations. The diminished synthesis and accumulation of glycogen and glycolytic capacity in the lungs of fetuses of diabetic mothers has been related to reduction in surfactant level, which underlies respiratory distress syndrome frequently encountered in neonates of diabetic pregnancies.
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PMID:Effects of maternal diabetes on the development of carbohydrate-metabolizing enzymes, glycogen deposition and surface active phospholipid levels in fetal rat lung. 630 58

The flux of glucose through the pentose phosphate pathway, important in relation to the provision of ribose 5-phosphate for nucleotide and RNA synthesis, was decreased by 70% in the diabetic rat heart in parallel with a similar decreased flux through the glycolytic route. A common factor linking the decreased flux through these alternative routes is the known fall in cardiac hexokinase; in these experiments there is a 50% decrease in Type II hexokinase (EC 2.7.1.1.) in both soluble and particulate fractions. The level of fructose 2,6-bisphosphate, a regulator of phosphofructokinase activity, is decreased by 20% in the alloxan diabetic rat heart, this may be a significant additional factor in the marked decrease in the flux of glucose through the glycolytic route in the myocardium in diabetes.
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PMID:Regulation of alternative pathways of glucose metabolism in rat heart in alloxan diabetes: changes in the pentose phosphate pathway. 636 95

An RIA has been developed for rabbit muscle PFK, an allosteric enzyme which catalyzes the pacemaker reaction of glucose utilization. The assay which could accurately measure as little as 12 ng (37.5 fmol) of the tetrameric enzyme was applied to extracts of skeletal and cardiac muscle of animals subjected to four different nutritional conditions and to alloxan diabetes. The concentration of enzyme remained unchanged in all conditions: mean value in anterior tibial muscle was 2.99 microM (S.D., 0.20; N, 32); in left ventricle, 0.66 microM (S.D., 0.07; N, 29). It may be concluded that control of the reaction is mainly, if not exclusively, by allosteric phenomena and not by insulin- or nutrition-dependent changes in intracellular concentration of the enzyme.
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PMID:Intracellular concentration of skeletal and cardiac muscle phosphofructokinase in diabetic and normal animals. 644 31

Phosphofructokinase (ATP:D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) was partially purified from the livers of genetically diabetic mice (C57BL/KsJ-db) and their lean littermates (C57BL/KsJ). These genetically diabetic mice have been shown to be hyperglucagonemic and to exhibit symptoms resembling those of maturity-onset diabetes in humans. Two isoenzymes of phosphofructokinase were obtained after DEAE-Sephadex chromatography of extracts of livers from either normal or diabetic animals. One of these isozymes, peak II, from the genetically diabetic mice was shown to be more sensitive to ATP inhibition at physiological pH than the peak II isozyme from the normal animals. In addition, the peak II isozyme from the diabetic mice exhibited decreased affinity for fructose 6-phosphate. The altered kinetic properties of phosphofructokinase from diabetic animals are markedly similar to those recently reported for liver phosphofructokinase isolated from normal animals after glucagon treatment. Our results suggest that increased glucagon levels in diabetes may lead to altered regulation of phosphofructokinase in this disease.
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PMID:Increased ATP inhibition of liver phosphofructokinase from genetically diabetic mice. 644 14

The concentrations of glycolytic intermediates and adenine nucleotides were determined in erythrocytes from patients with diabetic ketoacidosis before and during insulin treatment. Ketoacidosis resulted in an increase in the levels of intermediates above the phosphofructokinase (PFK) step and a marked decrease in the levels of those below this step. Thus, a "crossover" point was seen at the PFK step in a crossover plot. This indicated that the rate of glycolytic flow during ketoacidosis was controlled by PFK and that the reduced level of 2,3-bisphosphoglycerate (2, 3-BPG) was attributed to the inhibition of this enzyme. In vitro studies revealed that acidemia is mainly responsible for the inhibition of PFK, whereas elevated levels of ketone bodies and free fatty acids have no direct bearing on it. Insulin administration produced hypophosphatemia within 8-12 h and it persisted for 24 h or longer. The levels of fructose-6-phosphate and glucose-6-phosphate were decreased transiently during this hypophosphatemic phase, while those of fructose bisphosphate and triose phosphates were increased. This indicated that PFK was activated. Thus, it is no longer reasonable to think that the inhibition of PFK is a factor responsible for a delay in normalization of the 2, 3-BPG level during the recovery phase. The levels of these glycolytic intermediates, including 2, 3-BPG, were normalized within 4 days by appropriate therapy.
Diabetes 1981 Apr
PMID:Alteration of glycolytic intermediary metabolism in erythrocytes during diabetic ketoacidosis and its recovery phase. 645 63


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