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

---

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

The effects of elevated glucose and Eicosapentaenoic acid (EPA, 20:5) on myoinositol uptake in human aortic smooth muscle cells (HASMC) were evaluated. Myo-inositol incorporation into HASMC was dependent on an active transport system via Na(+)-K+ ATPase activity based on the results with Na+ deprivation and Ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. In addition, EPA potentiated Na(+)-K+ ATPase activity of HASMC. Since EPA decrease glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate aortic smooth muscle cell function associated with diabetes.
...
PMID:Eicosapentaenoic acid enhances myo-inositol uptake in cultured human aortic smooth muscle cells. 801 41

Non-insulin-dependent diabetes mellitus (NIDDM) is a metabolic disease associated with abnormal insulin secretion, the underlying mechanisms of which are unknown. Glucose-dependent signal transduction pathways were investigated in pancreatic islets derived from the db/db mouse, an animal model of NIDDM. After stimulation with glucose (4-12 mM), the changes in intracellular Ca2+ concentration ([Ca2+]i) were different; unlike control islets, db/db islets lacked an initial reduction of [Ca2+]i and the subsequent [Ca2+]i oscillations following stimulation with 12 mM glucose. The severity of these defects in Ca2+ signaling correlated with the age-dependent development of hyperglycemia. Similarly defective glucose-induced Ca2+ signaling were reproduced in control islets by pre-exposure to thapsigargin, a selective inhibitor of endoplasmic reticulum (ER) Ca(2+)-ATPase. Estimation of ATPase activities from rates of ATP hydrolysis and by immunoblot hybridization with an antiserum directed against the sarco/endoplasmic reticulum Ca(2+)-ATPase both demonstrated that the ER Ca(2+)-ATPase was almost entirely absent from db/db islets. The effects of inhibition of ER Ca(2+)-ATPase on insulin secretion were also examined; a 4-day exposure of control islets to 1 microM thapsigargin resulted in basal and glucose-stimulated insulin secretion levels similar to those found in db/db islets. These results suggest that aberrant ER Ca2+ sequestration underlies the impaired glucose responses in the db/db mouse and may play a role in defective insulin secretion associated with NIDDM.
...
PMID:Defective glucose-dependent endoplasmic reticulum Ca2+ sequestration in diabetic mouse islets of Langerhans. 803 70

Metabolic and vascular factors have been invoked in the pathogenesis of diabetic neuropathy but their interrelationships are poorly understood. Both aldose reductase inhibitors and vasodilators improve nerve conduction velocity, blood flow, and (Na+,K+)-ATPase activity in the streptozotocin diabetic rat, implying a metabolic-vascular interaction. NADPH is an obligate cofactor for both aldose reductase and nitric oxide synthase such that activation of aldose reductase by hyperglycemia could limit nitric oxide synthesis by cofactor competition, producing vasoconstriction, ischemia, and slowing of nerve conduction. In accordance with this construct, N-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase reversed the increased nerve conduction velocity afforded by aldose reductase inhibitor treatment in the acutely diabetic rat without affecting the attendant correction of nerve sorbitol and myo-inositol. With prolonged administration, N-nitro-L-arginine methyl ester fully reproduced the nerve conduction slowing and (Na+,K+)-ATPase impairment characteristic of diabetes. Thus the aldose reductase-inhibitor-sensitive component of conduction slowing and the reduced (Na+,K+)-ATPase activity in the diabetic rat may reflect in part impaired nitric oxide activity, thus comprising a dual metabolic-ischemic pathogenesis.
...
PMID:The linked roles of nitric oxide, aldose reductase and, (Na+,K+)-ATPase in the slowing of nerve conduction in the streptozotocin diabetic rat. 804 Mar 41

We investigated the dose-dependent effects of prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and Na(+)-K(+)-ATPase (ATPase) activity in streptozocin-induced diabetic rats. At 10 micrograms/kg/day, OP ameliorated MNCV and NBF, but no ATPase activity, whereas at 30 micrograms/kg/day it increased MNCV and ATPase activity, but not NBF. These results suggested a possible direct metabolic effect of OP, at least at a certain dose, on ATPase activity independent of NBF. Since PGE1 exerts an effect on nerve cAMP content, we conducted an in vitro study to clarify the relationship of cAMP to the modulation of ATPase activity in diabetic nerves. We studied sciatic nerves isolated from 53 rats with streptozocin-induced diabetes that had exhibited hyperglycemia for 6 wk. OP increased the activity of ATPase and the accumulation of cAMP in a dose-dependent manner. Dibutyryl cAMP, a cAMP analogue, and aminophyline, which increases nerve cAMP content, enhanced ATPase activity in a dose-dependent manner. In addition, the increased activity of ATPase in diabetic nerves produced by OP was suppressed by a protein kinase inhibitor, H8. These results suggest that ATPase activity in diabetic nerves might be regulated or modified by cAMP and, possibly, by protein kinase A, a finding that is important for clarifying the pathogenesis of diabetic neuropathy and for developing new approaches to treatment.
...
PMID:Metabolic effect of PGE1 analogue 01206.alpha CD on nerve Na(+)-K(+)-ATPase activity of rats with streptozocin-induced diabetes is mediated via cAMP: possible role of cAMP in diabetic neuropathy. 806 85

The temporal pattern of changes in the specific activities of retinal Na+, K(+)-ATPase (Na, K-ATPase) and Mg(2+)-ATPase (Mg-ATPase) were determined at several time intervals following the onset of diabetes in streptozotocin-induced diabetic (STZ: at 1, 2, 4 and 6 months) Long-Evans hooded rats, spontaneously diabetic Zucker diabetic fatty (ZDF: at 1, 2 and 4 months) rats and their age-matched controls. These animals were utilized as models for insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), respectively. Na, K-ATPase specific activity, using 10(3) M ouabain, was decreased (-6% to -14%) at all time points after the appearance of hyperglycemia in the ZDF rat, but was reduced only after 4 and 6 months in the STZ rat (-8% and -14%, respectively). In contrast, Mg-ATPase activity was significantly increased (13%) after 4 months in the ZDF rat and after 6 months in the STZ rat (8%). The concentration-dependent inhibitory effects of ouabain (10(-9) to 10(-3) M) on the activity of Na, K-ATPase in diabetic rats and age-matched controls was used to assess the time-dependent effects of diabetes on the alpha 3-high ouabain affinity or the alpha 1-low ouabain affinity retinal Na, K-ATPase isozymes. The retinal Na, K-ATPase activity for the alpha 3 isozyme was significantly lower at all times examined for the ZDF (-5% to -26%) and STZ-induced diabetic rats (-8% to -14%). This was reflected in the markedly decreased half-maximal inhibitory concentrations (IC50) of ouabain for the alpha 3 isozyme. For example, after four months of diabetes, the mean +/- SEM IC50 values were 12 +/- 3 nM in the STZ rats and 48 +/- 6 nM in the age-matched controls and 19 +/- 3 nM in the ZDF rats and 30 +/- 4 nM in the age-matched controls. In contrast, the activity of the alpha 1 isozyme was slightly, but significantly, decreased at 2 and 4 months in the ZDF rats (-4% to -7%) and after 4 and 6 months in the STZ-induced diabetic rats (-3% to -9%) while the IC50 values were unchanged. Moreover, the Hill coefficient for the alpha 3 isozyme was decreased in both diabetic groups while it was unchanged for the alpha 1 isozyme.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Alterations in retinal Na+, K(+)-ATPase in diabetes: streptozotocin-induced and Zucker diabetic fatty rats. 813 34

The effect of moderate hyperglycemia on renal ATP production and ATPase activity of rat fetus was investigated using the experimental procedure of maternal continuous infusion of glucose during the last 5 days of gestation. Glucose-infused mothers and their fetuses showed a high level of glycemia (8.8 and 5.5 mM, respectively) and a high level of insulinemia (3 times higher than in controls). No change in either ATP or ADP concentration was detectable but an increase in NaK ATPase activity occurred without any change in Mg ATPase activity. These modifications should be the result of an enhanced Na/glucose cotransport leading to an enhanced extrusion of Na at the basolateral membrane. These results indicate that immature kidney is able to increase NaK ATPase activity to maintain Na homeostasis.
...
PMID:Effect of maternal hyperglycemia on NaK ATPase activity in fetal rat kidney. 829 40

This study is an attempt to assess the role of dietary supplementation in the treatment and prevention of diabetic peripheral neuropathy. The authors developed an animal model system to study this problem. Animals given streptozotocin to induce a type I diabetic state showed elevated glucose levels and decreased body weight. Analysis of the sciatic nerve revealed a decrease in nerve conduction velocity and Na(+)-K(+)-ATPase activity. The activity of protein kinase C, another component of the nerve transmission process, was also affected by the diabetic state. The dietary intervention of polyunsaturated fatty acids seemed to revert some of these changes toward normal.
...
PMID:Polyunsaturated fatty acid supplementation in peripheral neuropathy. 836 34

The influence of elevated glucose concentration on resting membrane voltage, electrogenic Na(+)-K(+)-ATPase, and ATP-sensitive potassium channels (KATP channels) was studied in cultured bovine retinal capillary pericytes using conventional microelectrodes. The resting membrane voltage in cells grown in medium containing 5 mM glucose (control) averaged -27 +/- 1.2 mV (mean +/- SE, n = 26) and was not different from cells grown in medium containing 22.5 mM glucose (-26 1.2 mV, n = 26). Addition of ouabain (10(-4) M), a specific inhibitor of the Na(+)-K(+)-ATPase, depolarized the membrane potential by 3.6 +/- 0.4 mV (n = 10) in cells grown under control conditions and 0.7 +/- 0.2 mV (n = 6) in cells grown under elevated glucose conditions. Thus, electrogenic activity of the Na(+)-K(+)-ATPase was significantly (P < 0.0001) reduced to 19% compared with control conditions. Electrogenic Na(+)-K(+)-ATPase activity could be partially restored (ouabain-induced depolarization delta V = 2.0 +/- 0.2 mV, n = 6) in cells grown with high glucose in the presence of the aldose reductase inhibitor tolrestat (10(-5) M). The potassium channel opener Hoe 234 (10(-6) M) induced membrane potential hyperpolarization in control cells (delta V = 7.3 +/- 1.2 mV, n = 13), which could be completely inhibited by the KATP channel blocker glibenclamide (10(-7) M, n = 5). This indicates that pericytes possess KATP channels. The effect of KATP channels on membrane voltage was not significantly changed (P = 0.16) in cells cultured under high-glucose conditions (delta V = 9.6 +/- 2.0 mV, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of elevated glucose concentration on membrane voltage regulation in retinal capillary pericytes. 839 57

Glucose-induced insulin secretion is desensitized during long-term exposure of pancreatic islet beta-cells to elevated glucose levels. This study characterizes an in vitro model of glucose-induced desensitization in cultured isolated islets of the rat. Insulin secretion in desensitized islets cultured with 11 mM glucose for 4-7 days was progressively reduced compared with the normal freshly isolated (fresh) islets. When desensitized islets were returned to a basal concentration of glucose (5.5 mM) for up to 2 h, the glucose sensitivity of insulin secretion was restored to normal (recovered islets). Carbachol and L-arginine also reversed the effects of desensitization. However, basal insulin release was elevated in desensitized and recovered islets. Sodium-dependent myo-inositol uptake was reduced during desensitization by up to 49% within 4 days. myo-Inositol uptake was restored to normal in a time-dependent manner during recovery of islets at 5.5 mM glucose. The recovery of myo-inositol uptake paralleled that of insulin release. The apparent transport constant for myo-inositol uptake was significantly increased during desensitization, whereas the maximum uptake was not changed. myo-Inositol supplementation (35 or 250 microM) during islet culture did not alter myo-inositol uptake or insulin secretion in desensitized islets. Na(+)-K(+)-ATPase activity, but not 5'-nucleotidase activity, in desensitized islets was also inhibited by 65 and 47% when compared with fresh islet and recovered islet Na(+)-K(+)-ATPase activity, respectively. Thus, cultured islets represent an appropriate model to study biochemical parameters associated with the onset and reversibility of glucose desensitization of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Insulin secretion, myo-inositol transport, and Na(+)-K(+)-ATPase in glucose-desensitized rat islets. 839 25

The present experiments were undertaken to assess the influence of preischemic hypo- or hyperglycemia on the coupling among changes in extracellular K+ concentration (K+e) and in cellular energy state, as the latter is reflected in the tissue concentrations of phosphocreatine (PCr), Cr, ATP, ADP, and AMP, and in the calculated free ADP (ADPf) concentrations. The questions posed were whether the final release of K+ was delayed because the extra glucose accumulated by hyperglycemic animals produced enough ATP to continue supporting Na(+)-K(+)-driven ATPase activity, and whether the additional acidosis altered the ionic transients. As expected, preischemic hypoglycemia shortened and hyperglycemia prolonged the phase before K+e rapidly increased. This was reflected in corresponding changes in tissue ATP content. Thus, hypoglycemia shortened and hyperglycemia prolonged the time before the fall in ATP concentration accelerated. When tissue was frozen at the moment of depolarization, the tissue contents of ATP were similar in hypo-, normo-, and hyperglycemic groups, approximately 30% of control. This suggests that hyperglycemia retards loss of ion homeostasis by leading to production of additional ATP. However, hyperglycemia did not reduce the rate at which the PCr concentration fell, and the ATP/ADPf ratio decreased. There were marked differences in the amount of lactate accumulated between the groups. Thus, massive depolarization in hypoglycemic groups occurred at a tissue lactate content of approximately 4 mM kg-1. This corresponds to a decrease in intracellular pH (pHi) from approximately 7.0 to approximately 6.9. In the hyperglycemic groups, depolarization occurred at a lactate content of about 12 mm kg-1, corresponding to a pHi of approximately 6.4.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Coupling of energy failure and dissipative K+ flux during ischemia: role of preischemic plasma glucose concentration. 843 10


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---