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

Measurements have been made of the tissue content of phosphoribosyl pyrophosphate (PPRibP) and of a range of metabolic intermediates involved in the energy charge of the cell, the glycolytic and pentose phosphate pathways, and of the activity of the enzymes of the pentose phosphate pathway and of PPRibP synthetase (EC 2.7.6.1) in the livers of normal, diabetic, insulin-treated diabetic and starved rats and in livers of rats previously starved and then re-fed with high-fat or high-carbohydrate diets. Diabetes, starvation and high-fat diet all caused a fall in the hepatic PPRibP content, whereas insulin treatment and high-carbohydrate diet raised the tissue content. A positive correlation was shown between the PPRibP content and ATP, energy charge and the cytosolic [NAD+]/[NADH] quotient. A positive association between the PPRibP content and the flux of glucose through the pentose phosphate pathway and the synthesis of ribose 5-phosphate via the oxidative enzymes of that pathway, including ribose-5-phosphate isomerase (EC 5.3.1.6), was also observed. A negative correlation was found between the ADP, AMP and Pi contents, and no correlation existed between PPRibP content and the enzymes of the non-oxidative branch of the pentose phosphate pathway. There was no correlation between hepatic PPRibP content and the activity of PPRibP synthetase measured in vitro. These results are considered in relation to the control of PPRibP synthetase in the liver in vivo.
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PMID:Hepatic phosphoribosyl pyrophosphate concentration. Regulation by the oxidative pentose phosphate pathway and cellular energy status. 244 9

We evaluated the effects of phenobarbital, an inducer, on plasma glucose and serum immunoreactive insulin levels and on hepatic glucose and drug metabolism using an animal model of non-insulin dependent diabetes mellitus. Genetically obese (ob/ob) mice, characterized by hyperglycaemia, hyperinsulinaemia, fatty liver and obesity were selected. The impairment of diabetic state with age was associated with increased activities of NADPH producing enzymes, whereas mixed function oxidase system remained unaltered. Phenobarbital reduced serum immunoreactive insulin and plasma glucose levels and decreased gluconeogenesis. Hepatic glucose phosphorylating enzyme activity increased and glucose releasing enzyme activity decreased. The demand for NADPH in drug oxidation reactions, caused by the induction phenomenon, was reflected in the elevated activities of the NADPH producing enzymes in pentose phosphate pathway and in the activities of isocitrate dehydrogenase and malic enzyme from mitochondrial oxidation reactions. Glucose metabolism of lean littermates indicated that phenobarbital induction normalizes impaired intracellular glucose handling but leaves normal glucose metabolism unaltered. Hepatic glucose production rate was related to plasma glucose, NADPH producing enzyme activities and cytochrome P450 content in the obese and lean mice.
Diabetes Res 1989 Feb
PMID:Effects of enzyme induction therapy on glucose and drug metabolism in obese mice model of non-insulin dependent diabetes mellitus. 250 Oct 61

DHEA, a steroid precursor of androgens and estrogens has also an inhibitory effect on several enzymes, namely on 11 beta-hydroxylase, NADH oxidase and glucose 6-phosphate dehydrogenase. The latter is the rate limiting enzyme of the pentose phosphate cycle. This metabolic pathway provides the cells with extramitochondrial NADPH and pentose phosphates. NADPH is used for the synthesis of fatty acids and steroids. Together with ribose 5-phosphate, NADPH (as coenzyme of folate reductases) is required for the synthesis of nucleic acids. A deficient production of DHEA has been found to be responsible for several diseases obesity, diabetes type 2, hypertension, arteriosclerosis and hyperuricemia as well as malignant growth (low DHEA syndrome). DHEA administration favourably modified several of these metabolic disorders. These studies were started in our laboratory in 1962 and stopped in 1976 because we were short of DHEA. At that time the response to our results was rather theoretical, but the last years a new wave of interest in DHEA called for two consecutive symposia, where important findings were presented (Paris in January and Jena in April 1989). It is a damage that this new trend, started in our laboratory, could not be pursued up to now without interruption.
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PMID:[Dehydroepiandrosterone. Renaissance after 13 years]. 252 67

31P NMR was used to study the erythrocytes of three patients who exhibited a familial multisystem disease characterized by fatty liver, diabetes and nonspherocytic hemolytic anemia of unknown etiology. 31P NMR measurements disclosed an abnormally high level of intracellular inorganic phosphate (Pi) and an abnormally low level of ATP in the erythrocytes 6 h after blood withdrawal from proband (I-1). This finding suggested that ATP was markedly decreased in the red cells of this proband, as compared with those of normal subjects. Time-dependent changes of 31P NMR spectra of the erythrocytes from the two daughters (II-1, II-2) of the proband demonstrated clearly an enhanced decomposition of ATP with a concomitant increment of Pi. Several ATP-consuming enzymes in erythrocytes, such as those in the Embden-Meyerhof system, pentose phosphate pathway enzymes, Na+, K(+)-ATPase and Ca2+, Mg2(+)-ATPase, were within normal limits of activity, but Mg2(+)-ATPase was drastically above the normal limit. The Mg2(+)-ATPase activity was 3 times higher in the red cell membranes of these patients than in those from normal subjects.
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PMID:An interesting syndrome of hemolytic anemia, degeneration of the liver and diabetes associated with a high red cell Mg-ATPase, detected by 31P NMR spectroscopy. 253 4

A carbohydrate disturbance or diabetogenic effect may occur even in people with normal metabolism as an undesired side effect with a great number of drugs. According to present nomenclature a distinction should be made between a "decrease of glucose tolerance" and the appearance of a (manifest) "diabetes mellitus." Instead the term "borderline diabetes" is often used in American literature. Particularly with already existing glucose tolerance disturbances, or hereditary disposition, a further deterioration can lead to diabetes mellitus that may not always disappear after discontinued use of the drug. In this context, the glucocorticoids, the saluretics and the oral contraceptives have special clinical interest. In a table are listed several drugs having a minor, or only sporadically observed, or questionably unfavorable influence on glucose tolerance. Some contain diabetogenic toxins and chemical substances that are used for experimental diabetes inducement (in animals). Extensive literature concerning the influence of female sexual hormones or oral contraceptives on the carbohydrate metabolism seems contradictory. Several mechanisms are discussed: peripheral insulin resistance, increased secretion of growth hormones and insulin, increased peripheral insulin decomposition, and inhibition of glucose decomposition via the pentose-phosphatic shunt. Glucose tolerance disturbances caused by oral contraceptives are described by some authors as occurring in 25% to 75% of all cases. Other authors found no or only rarely such an effect. The composition of the test group, the kind of ovulatory inhibitor, and the length of usage period evidently play a great role. Earlier, the estrogens, especially for higher dosages, were attributed a diabetogenic effect. However, lately the gestagens have come more to the fore. After many years of pill usage, a greater incidence of pathological glucose tolerance was registered for combination than for sequential preparations. It would appear that for (younger) diabetics (without late complications) that the most suitable contraceptive should consist of a sequential preparation with a low estrogen admixture (below 50 mg). Which gestagen and which dosage would result in the smallest long-term effect on glucose tolerance remains to be clarified.
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PMID:[Drug-induced diabetes]. 289 32

The present study examined the effect of the aldose reductase inhibitor Statil (ICI 128436, ICI, Cheshire, U.K.) on the levels of metabolites and activities of enzymes involved in the glycolysis, polyol pathway and pentose phosphate pathway and on the flux of radioactive glucose through these pathways in kidney of streptozotocin diabetic rats. In kidneys of diabetic rats of 30 days duration the level of sorbitol was increased by +82% and fructose concentration was raised by +42%. After treatment with Statil for 9 days (reversal study) a significant fall in kidney sorbitol concentration and kidney fructose concentration was found. Lactate and UDP-glucose concentrations which were both significantly raised in diabetes by +80% and +23% respectively decreased by 20% after Statil treatment, together with a decline in UDP-glucose dehydrogenase activity. Aldose reductase and sorbitol dehydrogenase activities were also significantly lowered by Statil. In the reversal study there was no significant effect of Statil on the flux of glucose via alternative routes in the kidney cortex. In kidneys of diabetic rats of 9 days duration, the level of sorbitol increased by +61% and the concentration of fructose was raised by +30%. The treatment with Statil (25 mg/kg) from the day of induction of diabetes (prevention study) prevented the accumulation of sorbitol, fructose and UDP-glucose. The increase in the incorporation of radioactive glucose through the pentose phosphate pathway seen in diabetes was less marked in the renal cortex of diabetic rats treated with Statil ab initio.
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PMID:The effect of aldose reductase inhibitor Statil (ICI 128436) on the glucose over-utilization in kidney of diabetic rats. 296 32

The activities of enzymes of the glycolytic route, the pentose phosphate pathway and NADPH-linked enzymes have been measured in the kidneys of genetically obese (ob/ob) mice and their lean litter mates. The renal content of glucose 6-phosphate (G6P), fructose 6-phosphate (F6P), fructose 1,6-bisphosphate (Fru-1,6-P2) and fructose 2,6-bisphosphate (Fru-2,6-P2) were also measured. Increases were found in hexokinase and enolase with an upward trend in pyruvate kinase in the ob/ob mouse kidney; a significant decline in malic enzyme was also seen. The renal content of G6P and Fru-1,6-P2 increased. There was no renal hypertrophy despite a degree of hyperglycaemia, which was, however, considerably below that observed in experimental diabetes. Comparison of the renal changes in the hyperglycaemic-hyperinsulinaemic ob/ob mice with the hyperglycaemic-hypoinsulinaemic diabetic group showed two distinct groupings. Firstly, changes which were similar in the two groups included: increases in hexokinase, G6P and Fru-1,6-P2, and a decrease in malic enzyme. Secondly, opposite changes were seen in enolase and in enzymes at the G6P crossroads, phosphoglucose isomerase and phosphoglucomutase. The elevated hexokinase and G6P in both ob/ob and diabetic groups may be involved in the eventual accumulation of basement membrane material in the glomerulus which is a common feature of the two conditions.
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PMID:Regulation of pathways of glucose metabolism in the kidney. The activity of the pentose phosphate pathway, glycolytic route and the regulation of phosphofructokinase in the kidney of lean and genetically obese (ob/ob) mice; comparison with effects of diabetes. 297 63

This study examines the effect of an aldose reductase inhibitor (sorbinil) on the flux of specifically labeled glucose through alternative pathways of metabolism in the lens of normal and diabetic rats 1 wk after the induction of diabetes with alloxan. In the diabetic rat lens, there was an apparent increase in the flux of glucose through the pentose phosphate pathway (PPP), as measured by the difference in the yields of 14CO2 from [1-14C]glucose and [6-14C]glucose [C1-C6], this value was 0.087 +/- 0.005 and 0.263 +/- 0.034 mumol X g lens-1 X h (mean + SE of 6 values) for control and diabetic rats, respectively; sorbinil treatment decreased the values to 0.065 +/- 0.008 and 0.171 +/- 0.028, respectively. With glucose tritiated on carbon 2 or 3, it has been shown that the flux of glucose through the polyol route is increased, whereas the flux through the glycolytic pathway is decreased in the diabetic rat lens; both are restored toward normal in the sorbinil-treated diabetic group. These results suggest that the dual effects of diabetes in increasing the lens content of glucose and glucose 6-phosphate and the flux of glucose in the polyol pathway will result in an increased utilization of NADPH and production of NADH, factors favoring the flow of glucose through the PPP and restricting the glycolytic route in the diabetic rat lens. The inhibition of aldose reductase by sorbinil tends to normalize the redox state of the nicotinamide nucleotides, reimposing the NADPH limitation on the PPP and increasing the availability of NAD+ for the glycolytic route.
Diabetes 1986 Nov
PMID:Effect of aldose reductase inhibitor (sorbinil) on integration of polyol pathway, pentose phosphate pathway, and glycolytic route in diabetic rat lens. 309 2

Activity of pentose phosphate pathway in the intima grown inside vascular prosthesis was studied in alloxan diabetic rabbits. Ratio of 14CO2 production from 1-14C-glucose and 6-14C-glucose was 7.8 in the nondiabetic group and 78.9 in the diabetic group. Statistically positive correlation was found between the ratio and the levels of blood glucose or plasma triglyceride. These results suggest that pentose phosphate pathway in the vascular intima is active, and enhanced to a great extent in diabetes.
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PMID:Enhancement of pentose phosphate pathway in vascular intima from diabetic rabbit. 313 97

Evidence for differences in the mechanism of renal growth in experimental diabetes and compensatory hypertrophy after unilateral nephrectomy (UN) has been obtained from measurements of the activity of enzymes of the de novo and salvage pathways of purine synthesis in the kidneys of diabetic and UN rats and in doubly lesioned animals. In diabetes, the activity of enzymes of both pathways increased. No effect of UN on the activity of any of these enzymes was observed, nor was the effect of the double lesion greater than the effect of diabetes alone. The activity of the pentose phosphate pathway increased in diabetes but not as a result of UN. Again, the effect of the double lesion was no different from that of diabetes alone. These results indicate that the accretion of nucleic acids in diabetes involves a larger component of de novo synthesis, contrasting with UN, where depressed breakdown may play a significant role.
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PMID:Enzymes of the de novo and salvage pathways of purine synthesis in renal hypertrophy. Contrasting effects of early diabetes and unilateral nephrectomy. 323 21


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