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)

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

Human very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoproteins (HDL2 and HDL3) were glycosylated in vitro by incubation with high concentrations of glucose and glucose-6-phosphate. Glycosylated lipoproteins showed enhanced mobility on agarose electrophoresis when compared to control lipoproteins, samples treated with glucose-6-phosphate being more strongly affected. Extent of glycosylation of LDL was determined using thiobarbituric acid, LDL incubated with glucose exhibiting degrees of glycosylation 15-117% in excess of control. LDL incubated with glucose-6-phosphate however, gave values similar to those obtained with control incubations. Amino acid analysis of protein hydrolysates prepared from VLDL and LDL fractions incubated with glucose revealed reductions of up to 53% in the levels of free lysine when compared to control lipoprotein samples. The appearance of 2 novel peaks, probably corresponding to glucosyllysine, was also observed. The effects seen with glucose-6-phosphate however, were not as marked as expected. None of the other amino acids measured were decreased. These data show that plasma lipoproteins can be glycosylated in vitro and that an indication of the degree of glycosylation (by glucose) may be obtainable using thiobarbituric acid. Amino acid analysis revealed that the probable binding site for glucose on the apoproteins are the lysine residues. Although glucose-6-phosphate also binds to lysine residues the effects produced by this agent on plasma lipoproteins may also involve other mechanisms requiring further investigation.
Diabetes Res 1985 Nov
PMID:Non-enzymatic glycosylation of plasma lipoproteins in vitro. 407 97

The ability of glucose, glucose-6-phosphate, and glycerol phosphate to support incorporation of (14)C-palmitate into neutral lipid of adipose tissue has been studied in eight patients with maturity-onset diabetes. After two hours' incubation glucose and glucose-6-phosphate supported incorporation rates relative to glycerol phosphate of 30% and 44% respectively in diabetic tissue, whereas the corresponding rates in paired non-diabetic controls were 93% and 95%. This failure of adipose tissue to metabolize glucose in maturity-onset diabetes might be responsible for a delay in the clearance of glucose from the blood stream. Alternatively, a defect in glucose utilization might be due to tissue changes associated with maturity-onset diabetes.
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PMID:Defect in glucose utilization in adipose tissue of patients with maturity-onset diabetes. 576 28

The effect of nonenzymatic glycosylation on the susceptibility of fibrin to degradation by the specific fibrinolytic enzyme plasmin was evaluated using both a fibrin plate assay and a fluorogenic synthetic plasmin substrate assay. Data from both types of experiments demonstrate that nonenzymatic glycosylation reduces the susceptibility of fibrin to plasmin degradation. Acetylation and carbamylation have qualitatively similar effects, indicating that chemical modification of lysine amino groups is the underlying phenomenon responsible for the observed degradative defect produced by glucose. Experimental conditions that increased the rate of nonenzymatic protein glycosylation (higher monosaccharide concentration, glucose-6-phosphate) were associated with correspondingly greater degrees of resistance to degradation by plasmin. Such reduced degradation of nonenzymatically glycosylated proteins in vivo may contribute to the accumulation of fibrin and several other proteins observed in those tissues most frequently affected by the complications of diabetes.
Diabetes 1983 Jul
PMID:Nonenzymatic glycosylation reduces the susceptibility of fibrin to degradation by plasmin. 622 31

The mechanism by which exogenous glucose stimulates the incorporation of hepatic glucose-6-phosphate into glycogen in fasted rats has not been clearly delineated. We gave glucose intragastrically over a 3.5-h period during which liver glycogen was deposited at linear rates. Simultaneous primed continuous infusion of [2-3H] or [3-3H]glucose established that under these conditions absolute carbon flow through hepatic glucose-6-phosphatase was greatly suppressed. After 1 h, hepatic [UDP-glucose] and [glucose-6-phosphate] had fallen by 50-60% and the former remained low throughout the experiment. By contrast, [glucose-6-phosphate] rebounded to its initial value by 2 h and remained at this level during the subsequent hour. We interpret the data as follows. Exogenous glucose, in addition to acting as a precursor of liver glucose-6-phosphate, causes diversion of the latter away from free glucose formation and into glycogen synthesis. The fall in [UDP-glucose] is in accord with a glucose-induced activation of glycogen synthase, as proposed by Hers (Annu. Rev. Biochem. 1976; 45:167-89.). However, the fall-rise sequence of glucose-6-phosphate concentration constitutes the first direct evidence in vivo for simultaneous inhibition at the level of glucose-6-phosphatase.
Diabetes 1984 Feb
PMID:Evidence for suppression of hepatic glucose-6-phosphatase with carbohydrate feeding. 631 14

The metabolic basis for glycogen accumulation in the placenta of rats with diabetes induced by streptozotocin on day 12 of pregnancy was studied on days 15 and 20. On day 15 glycogen content of the placenta was 1.5-fold higher in the diabetic than in the control rats and this difference increased to greater than fivefold on day 20 of gestation whether calculated per g tissue or per total placenta. Accumulation of glycogen was associated with increased specific activities of both glycogen synthase and phosphorylase. The activities of these enzymes regulating synthase and phosphorylase activities and the activity of acid alpha-glucosidase were not significantly affected by diabetes. Glucose-6-phosphate concentration of the placenta was 67 and 23 nmol/g in diabetic and control rats, respectively. Incubation of placental homogenates with glucose increased the rate of inactivation of phosphorylase and activation of glycogen synthase. These results indicate that the enhanced glucogenesis in diabetes is not due to changes in the activities of these enzymes, as measured in vitro under standard conditions. The factors promoting glycogen accumulation in vivo are related to the abundance of glucose and glucose-6-phosphate as substrates for glycogen synthesis, which may also cause an increase in the activity ratio glycogen synthase a/phosphorylase a. In addition, the high intracellular glucose-6-phosphate concentration is likely to enable glycogen synthase b to contribute to glycogen synthesis.
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PMID:Mechanism of placental glycogen deposition in diabetes in the rat. 640 9

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

This study examined how the duration of experimentally induced diabetes affects myocardial metabolism. Both acutely (2-day) and chronically (30-day and 90-day) streptozocin (STZ)-diabetic rats exhibited hyperglycemia and hyperketonemia, while hyperlipemia was evident only in the chronically diabetic rats. The activity of succinate dehydrogenase was lower, whereas that of 3-hydroxyacyl-CoA-dehydrogenase was higher in the hearts of chronically diabetic rats. Although myocardial concentrations of glucose-6-phosphate, glycogen, and triacylglycerols were elevated in diabetes, the patterns of alterations differed between acute and chronic diabetes. The fructose-1,6-diphosphate/fructose-6-phosphate ratio declined progressively after STZ administration, which was not accompanied by a reciprocal increase in citrate levels, although citrate concentrations were elevated. Impaired glucose oxidation was more severe in the freshly isolated heart cells from 30-day than from 2-day diabetic rats. For a given substrate concentration, the oxidation rates of palmitate and 3-hydroxybutyrate were markedly reduced in myocytes from 30-day diabetic rats. However, they were similar to or even higher than the rates found in their control counterparts under conditions that reflected the respective in vivo concentrations of the substrates. Incubating isolated myocytes from 2-day diabetic rats in the presence of insulin only partially restored the impaired glucose oxidation. Insulin administered to the animals 4 h before the experiments restored the impaired glucose oxidation by the cells. Insulin in vitro or single injection in vivo had little or no effect on glucose oxidation in isolated myocytes from 30-day diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1984 Nov
PMID:The effects of acute and chronic diabetes on myocardial metabolism in rats. 650 Jan 87

To develop a technique for examining short term insulin effects in cultured human fibroblasts, the effect of insulin on glycogen synthase was determined. Fibroblasts contain detectable glycogen synthase activity which can be converted from the D form, dependent on glucose-6-phosphate for activity, to the 1 form, which is independent of glucose-6-phosphate, in the presence of insulin. In the basal state, about 6-20% of the glycogen synthase is independent activity. This increases to between 30 and 60 %1 activity after insulin stimulation. Stimulation is seen with insulin concentrations as low as 10-9 M, although maximal stimulation requires 10-7 - 10-6 M insulin. The effect of insulin is rapid, reaching a maximum within 20 min of incubation. Incubation the cells in fresh media without serum and glucose for up to 24 h before assay enhances the cellular response to insulin. Glucose has only a small, transient effect on the conversion of the enzyme from the D to the I form in the absence of insulin. These data demonstrate that human fibroblasts possess insulin-sensitive glycogen synthase, which may be used as a marker of metabolic response in disease states.
Diabetes 1980 Sep
PMID:Insulin activates glycogen synthase in cultured human fibroblasts. 677 26

125I-Insulin binding and insulin stimulation of glycogen synthase were examined in fibroblasts cultured from nine Type 1 (insulin-dependent) diabetic patients with age of onset of less than 42 years. In all cases specific insulin binding was qualitatively and quantitatively normal. Total 125I-insulin binding was elevated in cells from three patients with early onset diabetes (two with onset before age 1 year) due to an increase in 'non-specific' binding. When the ability of insulin to stimulate the conversion of the glucose-6-phosphate dependent to the glucose-6-phosphate independent form of glycogen synthase was measured, all cell lines responded, albeit to differing degrees. In general, the response of cells from diabetic donors was more variable than that of control fibroblasts. A slightly lower level of cellular glycogen was evident in the cells of the diabetic patients, and this was mirrored in slightly higher levels of the independent form of the enzyme. The average maximal level of the independent form of the enzyme also was higher in the diabetic patients' cells. Fibroblasts from one of the patients with very early onset diabetes had glycogen synthase levels that were markedly lower than in any other cell line examined. In summary, fibroblasts cultured from Type 1 diabetic patients do not show major defects in either insulin binding or action. A suggestion of subtle differences in the cells from the diabetic patients, particularly those with very early onset, is evident, however. Whether these are secondary to some primary genetic defect or represent some selection during culture remains to be determined.
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PMID:Insulin binding and activation of glycogen synthase in fibroblasts from Type 1 (insulin-dependent) diabetic patients. 681 51


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