Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response of rat quadriceps muscle fibers to chronic streptozotocin (STZ) diabetes was studied. Transverse sections of rectus femoris muscle from diabetic and weight-matched control rats were assayed for myofibrilar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR). A quantitative analysis was carried out by an automatic interactive analysis system focused on the fiber type size and distribution. STZ-induced diabetes caused important effects in this muscle, with changes in the distribution of oxidative enzyme reactions, type I fiber hypertrophy, and type II fiber atrophy, which was greater in type IIB than in type IIA. It is concluded that hypoinsulinism produces morphological alterations in proximal skeletal muscle fibers that are similar to those of neurogenic myopathy. Thus the pathological changes in these mammalian muscle fibers could explain the clinical syndrome seen in diabetic patients called "diabetic symmetrical proximal motor neuropathy," perhaps the least understood of the major neuropathic complications of diabetes.
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PMID:Proximal skeletal muscle alterations in streptozotocin-diabetic rats: a histochemical and morphometric analysis. 182 78

Adult rats injected with streptozotocin during the neonatal period displayed in the fed state moderate hyperglycemia. However, the percentages of glycated hemoglobin in erythrocytes and glycated lactate dehydrogenase in liver and pancreatic islets, as well as the sorbitol and glycogen content of the islets, were not significantly increased. Likewise, in intact islets, the ouabain-sensitive inflow of 86Rb+, and the ratio between 3H2O production from D-[2-3H]glucose and D-[5-3H]glucose were not different in control and streptozotocin-injected rats. These findings suggest that the alteration in both the mitochondrial catabolism of D-glucose and secretory response to the hexose previously documented in the islets of the latter animals are not attributable to factors such as the excessive nonenzymatic glycation of cytosolic proteins, sorbitol or glycogen accumulation, or impaired Na+, K(+)-adenosine triphosphatase (ATPase) activity. Although a contributive role of glucotoxicity in the impaired function of beta cell in this model of non-insulin-dependent diabetes should not be ruled out, it is speculated that streptozotocin might also cause a long-term damage of key mitochondrial dehydrogenases in the pancreatic beta cells and, possibly, their precursor cells.
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PMID:Neonatal streptozotocin injection: a model of glucotoxicity? 183 15

Osteopenia is a recognized complication of diabetes mellitus in humans and experimental animals. We recently found that tetracyclines prevent osteopenia in the streptozotocin-induced diabetic rat and that this effect was associated with a restoration of defective osteoblast morphology (Golub et al., 1990). The present study extends these initial ultrastructural observations by assessing osteoblast function in the untreated and tetracycline-treated diabetic rats. After a 3-week protocol, non-diabetic control and diabetic rats, including those orally administered a tetracycline, minocycline (MC), or a non-antimicrobial tetracycline analog (CMT), were perfusion-fixed with an aldehyde mixture; the humeri were dissected and processed for ultracytochemical localization of alkaline phosphatase (ALPase) and Ca-ATPase activities. Some rats from each experimental group received an intravenous injection of 3H-proline as a radioprecursor of procollagen, and the humeri were processed for light microscopic autoradiography. In addition, the osteoid volume in each experimental group was quantitatively examined by morphometric analysis of electron micrographs. During the diabetic state, active cuboidal osteoblasts in the endosteum of control rats were replaced by flattened bone-lining cells that contained few cytoplasmic organelles for protein synthesis (Golgi-RER system), and active transport (mitochondria). Treating diabetic rats with MC, and even more so with CMT, appeared to "restore" osteoblast structure. During diabetes, bone-lining cells incorporated little 3H-proline or secreted little labeled protein and produced only a very thin osteoid layer. Tetracycline administration to the diabetics increased both the incorporation of 3H-proline by osteoblasts and their secretion of labeled protein toward the osteoid matrix, in a pattern similar to that seen in the non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tetracycline administration restores osteoblast structure and function during experimental diabetes. 183 18

The effects of an aldose reductase (AR) inhibitor, elevated glucose and other compounds were evaluated on in vitro 2-[3H] myo-inositol (MI) uptake in cultured human endothelial cells (ECs). Significant AR activity was present in ECs (1,373 +/- 170 mumol/mg.min: incubated with 28 mM glucose for 48 hr). Since Na(+)-deprivation and the addition of Ouabain (5 mM) significantly reduced MI uptake, MI incorporation into ECs might be dependent on an active transport system via Na(+)-K+ ATPase activity. MI uptake was reduced significantly (21 +/- 6, 39 +/- 7% reduction) in the presence of excess glucose (27.5, 55 mM). However, addition of the AR inhibitor (ONO-2235 100 microM) prevented the glucose mediated inhibition of MI uptake (15 +/- 5, 21 +/- 6% reduction). These results suggest that inhibition of AR might prevent glucose-mediated toxicity via an increment of MI uptake.
Diabetes Res 1991 Oct
PMID:Effect of glucose and an aldose reductase inhibitor on myo-inositol uptake by cultured human endothelial cells. 184 13

myo-Inositol uptake by culture neuroblastoma cells at a concentration of myo-inositol less than 50 microM was largely Na+ dependent. Exposing neuroblastoma cells to media supplemented with increasing concentrations of myo-inositol resulted in an increase in myo-inositol accumulation and intracellular content, but myo-inositol incorporation into phospholipids was not increased. The data indicate that myo-inositol exists as separate pools in neuroblastoma cells, and one or more of these pools may contribute to phospholipid synthesis. Exposing neuroblastoma cells to an increased concentration of glucose caused a decrease in myo-inositol uptake by two separate mechanisms. Acute exposure of the cells to 30 mM glucose caused a myo-inositol concentration-dependent decrease in Na(+)-dependent myo-inositol uptake. We propose that the acute inhibition of myo-inositol uptake by glucose is likely due to a competitive type of inhibition. Chronic exposure of cells to media containing 30 mM glucose or 30 mM galactose also caused decreases in myo-inositol uptake and incorporation into inositol phospholipids and intracellular myo-inositol content. This decrease in myo-inositol metabolism persisted at a higher concentration of external myo-inositol than the acute inhibition. Supplementing media containing 30 mM glucose or 30 mM galactose with 250 microM myo-inositol restored myo-inositol metabolism and content. The inhibition of myo-inositol uptake by cells chronically exposed to increased concentrations of glucose or galactose was due to a noncompetitive type of inhibition that was blocked by the addition of sorbinil. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose or 30 mM galactose caused a decrease in Na(+)-K(+)-ATPase transport activity and resting membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Feb
PMID:Restoration of Na(+)-K+ pump activity and resting membrane potential by myo-inositol supplementation in neuroblastoma cells chronically exposed to glucose or galactose. 184 27

Sarcolemmal membranes were isolated from skeletal muscle by a sucrose density gradient method from rats with diabetes induced by a streptozotocin injection (65 mg/kg iv). The activities of Na(+)-dependent Ca2+ uptake and Ca2(+)-stimulated adenosine-triphosphatase (ATPase) in the sarcolemmal fraction from diabetic rats was higher than those from the control animals. These changes were apparent at various times of incubation (1-10 min) as well as at different concentrations of free Ca2+ (10(-7) to 10(-5) M) and developed during the third and/or fourth weeks after streptozotocin injection. ATP-dependent Ca2+ uptake in the sarcolemmal vesicles was also increased at 28 and 56 days after inducing diabetes. Treatment of diabetic animals with insulin for 14 days reversed the changes in Ca2+ transport activities toward the control levels. Sarcolemmal Mg2(+)-ATPase and Na(+)-K(+)-ATPase activities remained unchanged in diabetic preparations. Furthermore, no difference in the sarcolemmal phospholipid composition and sodium dodecyl sulfate-gel electrophoretic pattern was evident between the control and experimental groups. These results indicate a higher activity of the sarcolemmal Ca2+ transport, which may be associated with hyperfunction of the skeletal muscle in diabetic rats.
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PMID:Increased sarcolemmal Ca2+ transport activity in skeletal muscle of diabetic rats. 185 Feb 3

A myo-inositol-related defect in nerve Na(+)-K(+)-ATPase in experimental diabetes has been invoked in the pathogenesis of diabetic neuropathy, but the mechanism linking altered myo-inositol metabolism and Na(+)-K(+)-ATPase regulation in diabetic nerve is uncertain. Decreased Na(+)-K(+)-ATPase in diabetic rat nerve is normalized by aldose reductase inhibitors or dietary myo-inositol, which preserve normal nerve myo-inositol content in vivo. Decreased Na(+)-K(+)-ATPase in diabetic rabbit nerve is acutely reversed by exposure to protein kinase C agonists in vitro. This study explored the relationship between the myo-inositol-sensitive and protein kinase C-agonist-sensitive Na(+)-K(+)-ATPase defects in diabetic rat nerve. Ouabain-sensitive ATPase activity was measured in an enriched membrane fraction isolated from nondiabetic, streptozocin-induced diabetic, and myo-inositol-supplemented streptozocin-induced diabetic rats before and after the membranes were exposed to protein kinase C agonists in vitro. The decreased ouabain-sensitive ATPase activity in plasma membranes from untreated diabetic rats was increased after exposure to two structurally unrelated protein kinase C agonists; the normal ouabain-sensitive ATPase in plasma membranes from myo-inositol-supplemented diabetic rats was unaffected by protein kinase C agonists. The nonadditivity and implied equivalence of the Na(+)-K(+)-ATPase defect corrected by myo-inositol in vivo and by protein kinase C agonists in vitro are consistent with the postulated existence of a deficient myo-inositol-dependent phospholipid-derived protein kinase C agonist (presumably diacylglycerol) in diabetic nerve that regulates nerve Na(+)-K(+)-ATPase either directly or via a protein kinase C mechanism.
Diabetes 1991 May
PMID:Normalization of Na(+)-K(+)-ATPase activity in isolated membrane fraction from sciatic nerves of streptozocin-induced diabetic rats by dietary myo-inositol supplementation in vivo or protein kinase C agonists in vitro. 185 Jul 4

The ability of aldose reductase inhibitors to prevent the decline in neural Na+,K(+)-ATPase activity in diabetic rats has not been confirmed by all laboratories. In this study, the efficacy of two structurally different aldose reductase inhibitors was evaluated under different experimental conditions. Na+,K(+)-ATPase activity was measured in sciatic nerves from streptozocin-induced diabetic rats fed normal rodent chow or a chow supplemented with 68% sucrose. Nerve homogenates from chow-fed rats were prepared with a Dounce tissue grinder, whereas homogenates from the sucrose-fed rats were prepared with an Ultra-Turrax disperser. In the chow-fed rats, 4 weeks of untreated diabetes resulted in an increase in neural sorbitol and fructose, a decrease in myoinositol, and a 54% decline in Na+,K(+)-ATPase activity. Sorbinil administration (20 mg/kg/day) completely prevented the rise in sorbitol and fructose and the depletion of myoinositol, but did not prevent the decline in Na+,K(+)-ATPase activity. In diabetic rats fed the sucrose diet for 4, 6, and 8 weeks, the neural sorbitol and fructose levels were elevated, the myoinositol concentration declined, and the Na+,K(+)-ATPase activity was 26 to 28% below the control. Prevention or intervention treatment with sorbinil (20 mg/kg/day) or tolrestat (50 mg/kg/day) for 4 to 6 weeks prevented the alterations in sorbitol, fructose, and myoinositol, and also prevented the decline in Na+,K(+)-ATPase activity. In conclusion, prevention and intervention therapy with aldose reductase inhibitors prevented the decline in Na+,K(+)-ATPase in sciatic nerves of sucrose-fed streptozocin-diabetic rats that were homogenized with an Ultra-Turrax disperser, but not in sciatic nerves from streptozocin-diabetic rats fed normal rodent chow that were homogenized with a Dounce tissue grinder. These findings indicate that the assessment of aldose reductase inhibitor efficacy is dramatically affected by the type of nerve preparation assayed and/or the diet.
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PMID:Adenosine triphosphatase activity in sciatic nerve tissue of streptozocin-induced diabetic rats with and without high dietary sucrose: effect of aldose reductase inhibitors. 185 65

Left ventricular papillary muscle function, transmembrane action potentials, myosin adenosinetriphosphatase (ATPase) and isoenzyme distribution, and myocardial pathology were studied in hypertensive (H), diabetic (D), hypertensive-diabetic (HD), and control (C) rats. There was approximately 50% relative left ventricular hypertrophy in H and HD rats. Relative lung and liver weights were greater in HD rats. Peak velocity of shortening tended to decrease progressively in H, D, and HD rats. The duration of contraction and relaxation was markedly prolonged in Ds and HDs. The length-developed tension relation was blunted in HDs. The negative inotropic effect of verapamil was similar in all groups. Resting membrane potential and amplitude were decreased in D and HD rats. Action potential duration was increased in H, D, and especially HD rats. The shortening of action potential duration with increased stimulus frequency was greater in H, D, and especially HD rats than in Cs. Left ventricular myosin ATPase and V1 isoenzyme content decreased progressively in H, D, and HD rats. Right ventricular V1 isoenzyme content was not affected in H rats but was markedly decreased in D and HD rats. Left (and right) ventricular pathology was unchanged in rats with diabetes but was increased in rats with hypertension. These data suggest that the combination of myocardial pathology (due to hypertension) and cellular dysfunction (caused mainly by diabetes) may result in cardiomyopathy and congestive heart failure in the HD rat.
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PMID:Hypertensive-diabetic cardiomyopathy in rats. 213 24

Erythrocyte membranes drawn from diabetic patients with poor metabolic control have increased protein glycosylation and decreased Ca2(+)-ATPase activity. A significant relationship was found between these two parameters. Similar results were obtained when protein glycosylation and Ca2(+)-ATPase activity were measured in membranes from normal erythrocytes preincubated with glucose. In this condition, both parameters showed a clear time and dose dependence. Incubation of erythrocyte membranes instead of intact erythrocytes with glucose and glucose-6-phosphate strongly suggests that only the glycosylation of the membrane inner-surface proteins can affect Ca2(+)-ATPase activity. The simultaneous presence of 10 mM glucose and 5 mM ATP in the incubation medium did not affect the degree of erythrocyte membrane protein glycosylation but significantly blocked the inhibitory effect of glucose on Ca2(+)-ATPase activity. However, 5 mM ATP only partially blocked the inhibitory effect of 100 mM glucose, suggesting a competitive mechanism of glucose and ATP for the enzyme active site. Our results show that glycosylation of erythrocyte membrane proteins significantly inhibits Ca2(+)-ATPase activity. This effect could contribute to the development of the capillary closure process observed in diabetic patients. Furthermore, it could represent an index of a general impairment of enzyme function arising in cells chronically exposed to high glucose levels.
Diabetes 1990 Jun
PMID:Decreased Ca2(+)-ATPase activity after glycosylation of erythrocyte membranes in vivo and in vitro. 214 Aug 3


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