Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Neonatal streptozotocin injection: a model of glucotoxicity? 183 15

The role of extrarenal potassium homeostasis is well recognized as a major mechanism for the acute defense against the development of hyperkalemia. The purpose of this report is to examine whether or not the various mechanisms of extrarenal potassium regulation are intact in patients with end-stage renal disease (ESRD). The available data suggest that with the development of ESRD and the uremic syndrome there is impaired extrarenal potassium metabolism that is related to a defect in the Na,K-adenosine triphosphatase (ATPase). The responsiveness of uremic patients to the various effector systems that regulate extrarenal potassium handling is discussed. Insulin is well positioned to play an important role in the regulation of plasma potassium concentration in patients with impaired renal function. The role of basal insulin may be even more important than previously appreciated, since somatostatin infusion causes a much greater increase in the fasting plasma potassium in rats with renal failure than in controls. Furthermore, stimulation of endogenous insulin by oral glucose results in a greater intracellular translocation of potassium in uremic rats than in controls. Under at least two common physiologic circumstances, feeding and vigorous exercise, endogenous catecholamines might also act to defend against acute increments in extracellular potassium concentration. However, it is important to appreciate that the response to beta 2-adrenoreceptor-mediated internal potassium disposal is heterogeneous as judged by the variable responses to epinephrine infusion. Based on the evidence presented in this report, a regimen for the treatment of life-threatening hyperkalemia is outlined. Interpretation of the available data demonstrate that bicarbonate should not be relied on as the sole initial treatment for severe hyperkalemia, since the magnitude of the effect of bicarbonate on potassium is variable and may be delayed. The initial treatment for life-threatening hyperkalemia should always include insulin plus glucose, as the hypokalemic response to insulin is both prompt and predictable. Combined treatment with beta 2-agonists and insulin is also effective and may help prevent insulin-induced hypoglycemia.
 ...
PMID:Extrarenal potassium tolerance in chronic renal failure: implications for the treatment of acute hyperkalemia. 156 35

Recent data from our laboratory indicate that reduced membrane Ca-adenosine triphosphatase (ATPase) activity in non-insulin-dependent diabetics may be responsible for increases in intracellular calcium and, consequently, for elevated vascular resistance. Since obesity is frequently associated with hypertension, even before the development of overt diabetes, we evaluated blood pressure and erythrocyte cation levels and membrane Na/K-ATPase and Ca-ATPase in Zucker obese rats and their lean controls (n = 10 per group). Intra-arterial blood pressure, determined via a femoral cannula, demonstrated elevated systolic and diastolic pressure in the obese rats (P less than .05). There were no significant differences in Na/K-ATPase between groups, but there was a decrease in Ca-ATPase (P less than .01) in the obese rats and an increase in tissue and cellular calcium content (P less than .05). These data demonstrate a specific impairment in membrane Ca-ATPase activity in obese rats they may have caused the observed increase in cellular calcium and, consequently, increased blood pressure. These phenomena may result from impaired insulin activation of membrane Ca-ATPase in these insulin-resistant animals.
 ...
PMID:Impaired calcium metabolism associated with hypertension in Zucker obese rats. 216 30

Although insulin is known to elicit a positive inotropic effect in cardiac muscle preparations, very little is known concerning the mechanism of this action. In view of the crucial role played by the sarcoplasmic reticular (SR) calcium transport in cardiac contractile events, the effects of insulin on the pig heart SR were investigated. Insulin activated the SR Ca++-stimulated adenosine triphosphatase (ATPase) in a concentration-dependent manner (0.1 mU to 1 U/ml); maximal activation (125%) was seen at 0.1 to 1 U/ml of insulin. Kinetic studies revealed that the insulin-induced activation was due to an increase in the apparent Vmax of Ca++-stimulated ATPase without any alteration in the Km. Insulin was found to bind with SR membranes in a specific manner and this binding was rapid, saturable and displacable. The dose-related increase in the activation of Ca++-stimulated ATPase was related linearly (r = 0.98) to binding of insulin with SR membranes; 50% activation of Ca++-stimulated ATPase was found to occur at 13.5 fmol of insulin binding per mg of SR protein. When insulin was allowed to dissociate by a 100-fold dilution of the insulin-receptor complex, the activity of SR Ca++-stimulated ATPase also declined gradually. Furthermore, proteolytic digestion on the membrane with trypsin (3 micrograms/mg of protein) decreased both insulin binding as well as the increase in Ca++-stimulated ATPase activity by about 50%.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activation of heart sarcoplasmic reticulum Ca++-stimulated adenosine triphosphatase by insulin. 252 88

Low sodium and potassium adenosine triphosphatase (ATPase) activity has been proposed as a mechanism behind diabetic neuropathy. In this study the platelet ATPase activity and platelet noradrenaline efflux rate were determined in 47 insulin-dependent diabetes mellitus (IDDM) patients and 20 controls. Ulnar motor conduction velocities, tested in a subgroup, were lower in patients than in controls (52.7 +/- 1.3 m s-1 vs. 61.3 +/- 1.4 m s-1; P less than 0.001). Platelet ATPase activity tended to be increased in the patients compared with the controls (29.9 +/- 1.0 x 10(-3) min-1 vs. 26.9 +/- 1.1 x 10(-3) min-1; NS). In ulnar nerve function tested subjects, ATPase activity was higher in patients than in controls (31.2 +/- 1.7 x 10(-3) min-3 vs. 25.9 +/- 1.3 x 10(-3) min-1; P less than 0.01). The platelet noradrenaline efflux rate tended to be higher in patients with lower brake indices, a sign of autonomic neuropathy, than in controls (29.0 +/- 3.0 x 10(-3) min-1 vs. 21.2 +/- 0.9 x 10(-3) min-1; P less than 0.05). The platelet ATPase activity was not decreased in IDDM patients, however, a connection between diabetic autonomic neuropathy and platelet transmittor leakage was indicated.
 ...
PMID:Platelet sodium and potassium ATPase [corrected] activity and noradrenaline efflux rate in relation to autonomic and peripheral nerve function in insulin-dependent diabetic patients. 253 27

To explore metabolic changes associated with the sorbitol accumulation and myo-inositol depletion observed in glomeruli of rats with experimental diabetes, we examined total and ouabain-inhibited adenosine triphosphatase (ATPase) activity in glomeruli isolated from control and streptozocin (STZ)-diabetic rats. Glomerular Na/K-ATPase activity (ouabain-inhibited) was significantly reduced in diabetic animals, while total (composite) ATPase activity remained unchanged. Treatment with insulin partially restored the Na/K-ATPase activity. Administration of the aldose reductase inhibitor, sorbinil, which normalizes glomerular contents of both sorbitol and myo-inositol in diabetes, completely prevented the diminution of Na/K-ATPase activity. These results establish that glomerular Na/K-ATPase activity is reduced in acute experimental diabetes. The ability of sorbinil to prevent this decrease suggests that it is related to polyol accumulation and/or myoinositol depletion, although an effect of the drug unrelated to its aldose reductase inhibiting property has not been excluded. Since increased polyol pathway flux, decreased myo-inositol, and reduced Na/K-ATPase activity have also been described in peripheral nerve, another tissue in which typical diabetic complications characteristically occur, the consequences of these metabolic changes may be implicated in the pathogenesis of diabetic nephropathy.
 ...
PMID:Reduced glomerular sodium/potassium adenosine triphosphatase activity in acute streptozocin diabetes and its prevention by oral sorbinil. 299 80

The effect of insulin on total and ouabain-inhibited membrane-bound adenosine triphosphatase (ATPase) activity in renal glomeruli isolated from adult white rats was examined. In concentrations of 1-10 micrograms/ml, insulin significantly stimulated the ouabain-inhibited (Na+ + K+)-ATPase activity, without affecting total (composite) ATPase activity. These results, coupled with previous findings demonstrating that glomerular (Na+ + K+)-ATPase activity is reduced in acute streptozotocin diabetes, suggest that the renal glomerulus is a target tissue with respect to this biologic effect of insulin.
 ...
PMID:Insulin stimulates renal glomerular sodium-potassium adenosine triphosphatase activity. 300 70

In vascular smooth muscle, oxidative phosphorylation and glycolysis are independently regulated. Previous studies indicated that the independent regulation of these pathways was related to a compartmentation of carbohydrate metabolism. To further study carbohydrate metabolism, glucose transport and the incorporation of radiolabel from glucose into glycogen and lactate were measured after the oxidative and glycolytic pathways were independently altered. Ouabain stimulated mechanical activity, oxygen consumption, and glycogenolysis, whereas lactate production was decreased. Although glycogenolysis was substantial, glucose was the only substrate for lactate, indicating that intermediates derived from glycogen do not mix with those from glucose uptake. Thus glycogenolysis and glycolysis are carried out by independent enzymatic pathways. Insulin-stimulated lactate production and glucose transport without affecting the other parameters. Again, lactate was produced only from glucose. Phenytoin decreased isometric tension and oxygen consumption, whereas stimulating lactate production and glycogenolysis. Glycogen was the primary substrate for the lactate produced. Our findings indicate that the compartmentation of substrate utilization is ascribable to the coordination of glycogenolysis with increases in oxygen consumption and the coupling of glycolysis to the Na-K-adenosine triphosphatase. The coupling of independent energy providing pathways to specific endergonic processes indicates a mechanism by which cellular energetic efficiency may be optimized.
 ...
PMID:Compartmentation of carbohydrate metabolism in vascular smooth muscle. 303 Jan 31

The inhibition of glycolysis in tumor cells by methionine requires that the cells be incubated with methionine for several hours in the presence of serum. We now show that in the case of confluent rat-1 fibroblasts transfected with the ras gene the serum can be substituted by insulin and insulin-like growth factor I or II. No other growth factor tested was effective. In subconfluent ras cells additional growth factors (transferrin and high density lipoproteins) were required for maximal inhibition of glycolysis by methionine. Exploration of the mechanism of action of methionine revealed that the accumulation of [35S]methionine into rat-1 fibroblasts was only marginally increased by insulin. We propose that methionine inhibits an adenosine triphosphatase activity because addition of low concentrations of Nonidet P-40 greatly enhanced glycolysis even in the presence of methionine, suggesting that it did not affect the glycolytic enzymes directly. Methionine also affected growth both in monolayer and soft agar. Rat-1 fibroblasts transfected with the ras gene were markedly more sensitive to methionine than cells transfected with the myc gene.
 ...
PMID:Effect of growth factors and methionine on glycolysis and methionine transport in rat fibroblasts and fibroblasts transfected with myc and ras genes. 308 Dec 58

An ATP-dependent transport system which is active at concentrations of free Ca2+ in the submicromolar range has been identified in adipocyte plasma membranes. The system appears to represent the functional component of the high affinity insulin-sensitive calcium-stimulated, magnesium-dependent adenosine triphosphatase preveiously described in the same preparation (Pershadsingh, H. A., and McDonald, J. M. (1979) Nature 281, 495-497). This ATP-dependent Ca2+ transport pump was stimulated approximately 3-fold by the Ca2+-dependent regulatory protein, calmodulin. This effect was confined to the plasma membrane since a similar effect was undetectable in the fraction enriched in endoplasmic reticulum. Calmodulin stimulation was dose-dependent but saturable with half-maximal activation occurring at 0.72 microgram/ml (43 nM). Calmodulin appeared to stimulate the system primarily by decreasing the apparent half-maximal saturation constant for free Ca2+ from 0.20 +/- 0.04 microM to 0.07 +/- 0.01 microM (n = 3). The Hill coefficient increased from 1.6 +/- 0.2 to 3.2 +/- 0.6 (n = 3), thus showing an increased positive cooperativity which allows the pump to be activated by an exceedingly narrow Ca2+ threshold in the presence of calmodulin. The calmodulin stimulation of the plasma membrane Ca2+ extrusion pump in adipocytes, working in opposition to metabolic signals which increase cytoplasmic Ca2+, could constitute a self-regulating negative feedback device for maintaining a low steady state level of intracellular Ca2+. This feedback system may be of critical importance in regulation of cellular metabolism by insulin.
 ...
PMID:Calmodulin-sensitive ATP-dependent Ca2+ transport across adipocyte plasma membranes. 610 20


<< Previous 1 2 3 4 5 6 Next >>