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

The activities of hepatic enzymes involved in glucose phosphorylation and NADPH production were studied in male and female obese Zucker rats (fa/fa) and lean control animals (Fa/-). The fa/fa animals were heavier and had higher serum insulin levels than the lean rats. The glucokinase activity and the total glucose phosphorylation capacity were also higher in the obese animals. The activity of glucokinase correlated significantly with serum insulin levels. The glucose-6-phosphate phosphohydrolase activity was unchanged or slightly lowered in the obese rats. The activity of malic enzyme was elevated in the obese animals.
Diabetes Res 1989 Mar
PMID:Activity of hepatic glucose phosphorylating and NADPH generating enzymes in Zucker rats. 268 Feb 27

Transglutaminase activity in rat islet homogenates was increased after preincubation of the islets at high glucose concentration, and severely decreased after preincubation in the presence of either 1,2-bis(2-chloroethyl)-1-nitrosurea or 2-cyclohexene-1-one. The stimulatory action of glucose was still observed when the islets were preincubated in the absence or extracellular Ca2+. The enzymic activity was decreased by NAD+ or NADP+ but not NADH or NADPH, and inhibited by GSSG more than by GSH. These findings suggest that the glucose-induced activation of transglutaminase may be related to induction of a more reduced redox state with subsequent change in thiol-disulfide balance.
Diabetes Res 1986 Mar
PMID:Glucose-induced activation of transglutaminase in pancreatic islets. 287 59

The mechanism whereby hyperglycaemia inhibits neutrophil function is unclear. We have examined neutrophil killing of Candida albicans in the presence of increased concentrations of glucose and galactose. Killing was abolished in 50 mmol/l glucose and 10 and 50 mmol/l galactose. The oxidative phase of killing was examined using lucigenin-enhanced chemiluminescence. An increase in glucose concentration from 5 to 50 mmol/l produced a fall in chemiluminescence output from 128.5 +/- 16.8 (mean +/- SE) to 82.2 +/- 9.8 mV min (a reduction of 36%). These data suggest the existence of aldose reductase activity in neutrophils and using gas chromatography we have demonstrated the presence of sorbitol in extracts of diabetic neutrophils. As oxidative killing and sorbitol production are both NADPH-dependent the inhibition of killing is likely to be due to competition for this electron donor. This abnormality of neutrophil function may aggravate various infections in the patient with diabetes.
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PMID:Neutrophil sorbitol production impairs oxidative killing in diabetes. 295 Dec 17

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

Therapy with enzyme inducing drugs may improve glycemic control in patients with non-insulin-dependent diabetes mellitus. We evaluated the role of a mixed function oxidase system on glucose metabolism with an animal model. Rats were treated with an inducer (phenobarbital), an inhibitor (cimetidine) and a hepatotoxin (carbon tetrachloride) for a week to cause alterations in the liver. The mixed function oxidase system was assayed by determination of the cytochrome P-450 content and NADPH cytochrome c reductase in liver. Carbohydrate metabolism was evaluated by determining blood glucose, enzymes associated with glucose phosphorylation in the liver (glucokinase, hexokinase), glucose storage as glycogen and enzymatic delivery, glucose-6-phosphatase, and peripheral tissue by determining phosphorylating enzyme (hexokinase) and a key glycolytic enzyme (pyruvate kinase) and glycogen content in muscles. The therapy with the inducer enhanced glucose utilization in liver and storage in muscles. The inhibitor decreased the mixed function oxidase system, reduced glucose phosphorylating, but not gluconeogenetic enzymes, in the liver and increased glycolysis in muscles. Carbon tetrachloride, a hepatotoxin, impaired mixed function oxidase, glucose phosphorylating and delivering enzyme activity in liver, reduced blood glucose and caused glycogen accumulation in muscles. The function of liver microsomal enzyme system seems to be closely related to enzymatic glucose metabolism in the liver and muscles.
Diabetes Res 1987 Apr
PMID:Hepatic mixed function oxidase system and enzymatic glucose metabolism in rats. 304 Mar 22

Sorbinil (CP 45,634), a potent aldose reductase (AR) inhibitor, has the ability to normalize both sorbitol levels and functional parameters such as orthograde axonal transport and motor nerve conduction velocity in peripheral nerves of diabetic rats, which implicates flux through the polyol pathway in the pathophysiology of diabetic neuropathy. In order to understand more fully the role of this enzyme, it is important to determine the major cellular location of AR in peripheral nerve. Experiments were designed that have taken advantage of the observation that peripheral nerve axons degenerate distal to an injury site, while Schwann cells remain viable. One sciatic nerve in each experimental rat was chronically ligated (up to 6 weeks) before inducing diabetes by an intravenous (iv) injection of streptozotocin (STZ; 65 mg/kg). Two days after the STZ injection, both sciatic nerves were removed from each animal, and the ligated nerve was divided into proximal (Schwann cells and axons) and distal (Schwann cells only) portions before being processed for sorbitol determinations. The intact nerves and the proximal portion of the ligated nerves (having both Schwann cells and axons) retained the ability to accumulate sorbitol after STZ injection, while the distal portion (having Schwann cells only) lost this capacity 4 days after ligation. This lack of ability to accumulate sorbitol was not due to failure of the substrate (glucose) to reach the distal nerve segment. Additionally, homogenates of whole nerves and of proximal portions of ligated nerves were able to form sorbitol from glucose in the presence of NADPH while homogenates of distal portions of ligated nerves had lost approximately 85% of this activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies of aldose reductase using neuronal cell culture and ligated rat sciatic nerve. 308 10

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

Depletion of lens glutathione (GSH) occurs quickly and drastically following induction of diabetes or galactosemia in rats as well as in lens culture. The explanation for this dramatic loss of GSH has been investigated by many laboratories but the solution has been elusive. There are several possible causes for the change in the reducing power of the lens under hyperglycemia. (a) The enzyme glutathione reductase which reduces oxidized glutathione to GSH is inhibited. (b) The cofactor NADPH which both the aldose reductase of polyol pathway and glutathione reductase require becomes depleted under hyperglycemia to the point that there is an insufficient amount for glutathione reduction. (c) Membrane permeability is increased, due to osmotic-induced lens hydration. We explored all the above possibilities in the mechanism of GSH depletion and studied the effect of aldose reductase inhibitor (ARI) on osmotic change. We found that under hyperglycemic condition, there was no change in the enzyme glutathione reductase activity. There was an initial drop in NADPH level but there was sufficient remaining for glutathione reductase use. Both NADPH and glutathione depletion could be prevented completely by ARI. In addition, ARI could also prevent any hyperglycemic-induced abnormal transport and leakage of amino acids. We have therefore concluded that only the decreased membrane transport of amino acids which are needed for glutathione biosynthesis and the simultaneous loss of GSH through leaky membrane as initiated by the polyol pathway can be responsible for the drastic GSH depletion.
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PMID:Glutathione depletion in the lens of galactosemic and diabetic rats. 313 35

A decrease in glutathione content followed by a fall in ATP content of lens occurring at approximately 7 days after the onset of diabetes has been demonstrated in an earlier study. This pattern is repeated under more controlled conditions and at shorter time intervals, 24-48 hr, in lenses incubated in vitro under hyperglycemic conditions. Inclusion of aldose reductase inhibitors in the incubation medium not only prevented the accumulation of sorbitol and fructose but also prevented the decrease in glutathione and ATP. It is proposed that the drain on NADPH by the polyol pathway operating at high glucose concentrations results in a perturbation of the system for regenerating reduced glutathione. This aspect of polyol formation is considered to be deleterious to the lens in hyperglycemia, since it may contribute to free radical damage by depressing the system responsible for their removal.
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PMID:Antioxidant status in an in vitro model for hyperglycemic lens cataract formation: effect of aldose reductase inhibitor statil. 314 3

Increase in content of glucose in aorta as well as in reducing properties of NAD and NADP coenzymes and alteration in content of cofactor of the sorbitol pathway led to accumulation of sorbitol in streptozotocin-diabetic rats. Administration of nicotinamide into diabetic animals induced an increase in the ratios of NAD+/NADH and NADP+/NADPH, accompanied by a decrease in sorbitol formation occurring in the reaction catalyzed by aldose reductase and stimulation of the sugar oxidation in the reaction catalyzed by sorbitol dehydrogenase. Possible use of nicotinamide for prevention and treatment of vascular lesions in diabetes is discussed.
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PMID:[Nicotinamide coenzyme regulation of the sorbitol pathway of glucose metabolism in the aorta of rats with streptozotocin diabetes]. 315 51


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