Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondria isolated from livers of rats treated briefly with glucagon show an increased ATPase activity in the presence of appropriate concentrations of protonophoric uncouplers (Yamazaki, R. K., Sax, R.D., and Hauser, M.A. (1977) FEBS Lett. 75, 295-299). With the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) the effect of glucagon treatment was most evident at concentrations of uncoupler higher than required for maximal stimulation of ATPase in control mitochondria. In this range of FCCP concentrations that produced the greatest contrast in ATPase activity of control and hormone-stimulated mitochondria, there were no significant differences in delta pH, delta psi, or delta p between the two groups. The presence of added succinate in the ATPase assay system mimicked the effect of glucagon treatment, permitting greater activity at high concentrations of uncoupler without significantly affecting delta p. No significant effect of glucagon treatment or uncoupler concentrations on mitochondrial volumes was observed. Following treatment with glucagon, the mitochondria retained a greater content of Mg+ and K+ throughout the range of FCCP concentrations tested. In the upper range of FCCP concentrations there was appreciable loss of K+ from the mitochondria which was greater in control mitochondria than in mitochondria from glucagon-treated rats or in mitochondria assayed in the presence of succinate. The activity of the uncoupler-dependent ATPase was greatly stimulated by increased concentrations of potassium chloride in the assay medium without significantly diminishing the hormone effect. It is proposed that the intrinsic peptide inhibitor of ATPase is dissociated from the enzyme to an increased degree following glucagon treatment and that high levels of uncoupler inhibit by causing an increased association of the enzyme and its inhibitor.
 ...
PMID:The interaction of glucagon treatment and uncoupler concentration on ATPase activity of rat liver mitochondria. 623 34

The characteristics and kinetics of calcium uptake activity were studied in isolated hepatic microsomes. The sustained accumulation of calcium was ATP- and oxalate-dependent. Glucagon increased microsomal Ca2+ uptake upon either in vivo injection, or in vitro perfusion of the hormone in the liver. In contrast, the effect of insulin depended on the route of administration. Calcium accumulation by subsequently isolated hepatic microsomes increased when insulin was injected intraperitoneally whereas it decreased when the hormone was perfused directly into the liver. These effects of glucagon and insulin were dose dependent. When insulin was added to the perfusate prior to the addition of glucagon, insulin blocked the glucagon-stimulated increase in microsomal Ca2+ uptake. Cyclic AMP mimicked the effect of glucagon on microsomal Ca2+ accumulation when the cyclic nucleotide was perfused into the liver. The effects of glucagon and insulin on the kinetics of hepatic microsomal Ca2+ uptake were investigated. In microsomes isolated from perfused rat livers treated with glucagon the V of the uptake was significantly increased over the control values (12.2 vs. 8.6 nmol Ca2+ per min per mg protein, P less than 0.02). In contrast, the addition of insulin to the perfusate significantly decreased the V of Ca2+ uptake by subsequently isolated microsomes (6.8 vs. 8.3 nmol Ca2+ per min per mg protein, P less than 0.05). However, neither hormone had an effect on the apparent Km for Ca2+ (4.1 +/- 0.5 microM) of the reaction. The effect of these hormones on the activity of Ca2+-stimulated ATPase was also studied. No significant changes in either V or Km for Ca2+ of the enzymatic reaction were detected.
 ...
PMID:Characterization of the hormone-sensitive Ca2+ uptake activity of the hepatic endoplasmic reticulum. 624 28

The MDCK dog kidney epithelial cell line has been shown to retain the capacity for vectorial salt and fluid transport, sensitivity to growth regulation, and the ability to regenerate kidney tubular-like structures when injected into athymic nude mice. MDCK cells grown in tissue culture or in baby nude mice have the morphological properties of distal tubular cells, form tight and gap junctions, lack proximal tubular enzyme markers, and possess appreciable activities of Na+-K4-ATPase, ectoleucine aminopeptidase, and ectoalkaline phosphatase. Adenylate cyclase in intact cells is responsive to vasopressin, prostaglandins E1 and E2, and glucagon. Two Na+ transport systems have been characterized: a Na+-H+ antiport system, sensitive to amiloride inhibition, and a NaCl-KCl cotransport system, dependent on metabolic energy and sensitive to furosemide inhibition. Genetic techniques have been used to modify the properties of the cells. The results suggest that the MDCK cell line has retained the differentiated properties of the kidney epithelial cells of origin and that a clonally isolated cell possesses the receptor, transmission, and target enzyme systems necessary for the regulation of transcellular salt and fluid transport.
 ...
PMID:Growth and differentiated properties of a kidney epithelial cell line (MDCK). 625 47

The effects of insulin and glucagon on the (Na+-K+)-ATPase transport activity in freshly isolated rat hepatocytes were investigated by measuring the ouabain-sensitive, active uptake of 86Rb+. The active uptake of 86Rb+ was increased by 18% (p less than 0.05) in the presence of 100 nM insulin, and by 28% (p less than 0.005) in the presence of nM glucagon. These effects were detected as early as 2 min after hepatocyte exposure to either hormone. Half-maximal stimulation was observed with about 0.5 nm insulin and 0.3 nM glucagon. The stimulation of 86Rb+ uptake by insulin occurred in direct proportion to the steady state occupancy of a high affinity receptor by the hormone (the predominant insulin-binding species in hepatocytes at 37 degrees C. For glucagon, half-maximal response was obtained with about 5% of the total receptors occupied by the hormone. Amiloride (a specific inhibitor of Na+ influx) abolished the insulin stimulation of 86Rb+ uptake while inhibiting that of glucagon only partially. Accordingly, insulin was found to rapidly enhance the initial rate of 22Na+ uptake, whereas glucagon had no detectable effect on 22Na+ influx. These results indicate that monovalent cation transport is influenced by insulin and glucagon in isolated rat hepatocytes. In contrast to glucagon, which appears to enhance 86Rb+ influx through the (Na+-K+)-ATPase without affecting Na+ influx, insulin stimulates Na+ entry which in turn may increase the pump activity by increasing the availability of Na+ ions to internal Na+ transport sites of the (Na+-K+)-ATPase.
 ...
PMID:Insulin and glucagon stimulation of (Na+-K+)-ATPase transport activity in isolated rat hepatocytes. 626 50

In the perfused rat liver administration of glucagon was shown to result in a transiently increased uptake of K+, indicating the possible involvement of the Na+, K+-ATPase. Direct measurement of the activity of Na+, K+-ATPase revealed a two-fold stimulation of the enzyme by glucagon. The effect of glucagon on the activity of the enzyme was immediate. Simultaneously with the increase in the activity of the Na+, K+-ATPase, the activity of Mg2+-ATPase decreased. In order to evaluate whether the activation of the Na+, K+-ATPase by glucagon is related to the metabolic effects of the hormone, experimental conditions known to interfere with the activity of the enzyme were employed and glucagon stimulation of Ca2+-efflux, mitochondrial metabolism and gluconeogenesis were measured. K+-free perfusate, high K+ perfusate or ouabain interfered to varying degrees with the glucagon stimulation of these responses. The combination of K+-free perfusate and ouabain almost completely abolished the glucagon stimulation of all three parameters. These results demonstrate the glucagon stimulation of Na+, K+-ATPase and raise the possibility that the activation of the enzyme by glucagon might be a necessary link for the manifestation of its metabolic effects.
 ...
PMID:Glucagon stimulation of hepatic Na+, K+-ATPase. 628 3

In experiments on fasted, pentobarbital-anesthetized rats the effect of insulin (1 U X kg-1, followed by 0.05 U X kg-1 X min-1), glucagon (0.5 micrograms X kg-1 X min-1), and dibutyrylic cyclic AMP (DBcAMP) (0.5 mumol X kg-1 X min-1) on bile flow and composit8ion was examined. Infusion of these substances resulted in maximal increases only in the bile acid-independent bile formation, and insulin appeared to be a more powerful stimulant of bile production than glucagon or DBcAMP. When bile production was first stimulated maximally with glucagon or DBcAMP, supplementary infusion of insulin increased bile production significantly. When administration of glucagon or DBcAMP supplemented maximal infusion of insulin, only DBcAMP resulted in a further increase in bile production. Bile production was, however, increased by supplementary glucagon infusion, when a submaximal dosage of insulin was given. No additive effect of glucagon and DBcAMP on bile secretion was observed. The results suggest that glucagon induces choleresis in rats via liberation of cAMP and that the mechanisms of glucagon choleresis differ at least partly from those involved in insulin choleresis. The results are compatible with an insulin-produced inhibition of the adenylate cyclase and activation of the phosphodiesterase in the liver. In accordance with present knowledge of the biological effects of insulin and glucagon the choleretic response to both hormones may be secondary to stimulation of Na-K-ATPase located to the hepatocellular membrane.
 ...
PMID:Interaction of insulin, glucagon, and DBcAMP on bile acid-independent bile production in the rat. 629 19

Specific binding sites have been demonstrated to exist in the heart for several drugs and hormones such as beta-blocking agents, cardiac glycosides, catecholamines, insulin, glucagon and acetylcholine. The specific binding sites for cardiac glycosides in the human heart have certain properties which make it likely that they are the pharmacological receptors for the therapeutic and toxic actions of digitalis glycosides: they are located in the cell membrane and bind cardioactive steroids reversibly with high affinity: half-maximal receptor binding occurs at approximately 2 nM (approximately 1.5 ng/ml) for digoxin; potassium decreases receptor affinity, calcium increases it; specific binding of ouabain, digoxin or digitoxin is related to inhibition of (Na+ + K+)-ATPase activity--which is supposed to be the receptor enzyme for cardiac glycosides. Human left ventricle contains approximately 1.5 x 10(14) binding sites/g wet weight, right ventricle approximately 0.9 x 10(14). In disease the number of receptors may decrease (hypothyroid states, myocardial infarction) or increase (hyperthyroidism, chronic hypokalaemia). Certain drugs (such as phenytoin) or different temperatures or pH changes cause a change in digitalis-receptor affinity. Thus, the number of receptors and possibly their properties are subject to regulation in clinically relevant situations. Further investigations will probably reveal those pathophysiological states, which allow the explanation of toxicity or digitalis refractoriness.
 ...
PMID:The cardiac glycoside-receptor system in the human heart. 630 38

The intraperitoneal injection of glucagon or the intravenous infusion of oleic acid provoked a rapid change in the properties of rat liver mitochondrial ATPase. When mitochondria of treated animals were isolated an increase in ATPase activity was observed as well as a modification on the response to activators and inhibitors and to the sulfhydryl reagent N-ethylmaleimide. Sensitivity to the activators dinitrophenol or bicarbonate decreased, whereas the sensitivity to inhibitors KOCN and KSCN increased, and an inhibitory effect of N-ethylmaleimide appeared. These effects gradually disappeared when mitochondrial suspensions were kept at 10 degrees C, and after approximately 5 h ATPase from mitochondria of treated and control animals behaved almost identically. If the oxidizing agent dichlorophenolindophenol was added to the isolated mitochondria the effects induced by glucagon or fatty acids immediately disappeared. The activation caused by the reducing agent dithionite on ATPase activity in mitochondria from control animals did not take place in fresh mitochondria from treated animals; however, dithionite was effective in these latter mitochondria when tested 5 h later after keeping them at 10 degrees C. The intravenous infusion of oleic acid produced a rise in the [NADH]/[NAD+] and [Total flavin]/[FAD] ratios in mitochondria, and values double as those in the controls were observed; these values gradually approached those of the control mitochondria when kept at 10 degrees C; after 24 h these ratios were the same in mitochondrial suspensions from treated and nontreated animals. These results suggest that the modification of the properties of mitochondrial ATPase induced by glucagon or fatty acids might be mediated by a change in the mitochondrial redox state.
 ...
PMID:Effect of injected glucagon or fatty acids on mitochondrial ATPase. 632 87

Glucagon receptor levels, glucagon-stimulated and other forms of adenylyl cyclase activity, and regulatory component activity of adenylyl cyclase were determined in hepatic plasma membranes of rats administered streptozotocin without and with insulin to produce varying degrees of hyperglycemia. Receptor levels were assayed by direct binding of the specific probe [125I-Tyr10]-iodoglucagon; regulatory component activity was assayed by the capacity to reconstitute stimulatory regulation in deficient membranes from cyc- S49 murine lymphoma cells. In rats given 150 mg streptozotocin, glucagon stimulation of adenylyl cyclase as well as basal, sodium fluoride, 5' guanylylimidodiphosphate [GMP-P(NH)P] and Mn-dependent activities were reduced 50%, glucagon receptor levels but not affinity were reduced 67%, and regulatory component activity was decreased 50%. In addition, alpha 1-adrenergic receptors and 5'-nucleotidase were similarly reduced in diabetes. However, specific ouabain-inhibitable Na+, K+, ATPase activity was not altered by streptozotocin treatment. The streptozotocin-induced changes were noted within 24 h and became maximal by 120 h after its administration. All of these decreases were partially reversed by in vivo insulin treatment. DNA, cytochrome c oxidase, glucose-6-phosphatase, and N-acetyl-beta-glucosaminidase content in hepatic plasma membrane preparations were not substantially different in diabetic as compared with control animals. The data demonstrate that glucagon-mediated regulation of cyclic AMP formation is deranged in insulin deficiency owing to a combined decrease in receptors, derangement of the coupling mechanism intervening between receptor and adenylyl cyclase, and possibly, an altered basal effector system. Some of these changes appear to reflect a "desensitization-like" phenomenon which may or may not be attributable to the hyperglucagonemia of diabetes mellitus. There also appears to be a concurrent generalized decrease in several but not all plasma membrane receptor and enzymatic proteins. This may be the result of a number of processes among which is the accelerated proteolysis of uncontrolled diabetes.
 ...
PMID:Glucagon-stimulable adenylyl cyclase in rat liver. The impact of streptozotocin-induced diabetes mellitus. 632 32

Acute treatment of rats with glucagon increased the Vmax but did not change the Km (ATP) of uncoupler-activated ATPase in subsequently isolated hepatic mitochondria. The hormonal stimulation was evident in mitoplasts but not in submitochondrial particles nor after lysis of the mitochondria. The rate of Pi-ATP exchange of intact mitochondria was also increased by glucagon treatment. The hormonal stimulation of ATPase was dependent on concentration of the uncouplers, being absent at minimally effective concentrations while high concentrations inhibited the ATPase. Inhibitors of adenine nucleotide transport decreased ATPase activity without evidence of sigmoidicity in the response curves and produced linear Dixon plots indicating that the ATPase was limited by the rate of adenine nucleotide transport. Glucagon treatment did not change the number of binding sites for transport inhibitors. Glucagon stimulated the rate of transport of ATP as measured by accumulation of labeled nucleotide. This was found to be the consequence of an enlarged pool of exchangeable adenine nucleotides within mitochondria from glucagon-treated animals. This increase in mitochondrial nucleotides appears to explain a number of the effects of hormones on mitochondrial functions including the stimulation of uncoupler-activated ATPase activity.
 ...
PMID:The control of uncoupler-activated ATPase activity in rat liver mitochondria by adenine nucleotide transport. The effect of glucagon treatment. 644 11


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