Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rat pancreatic islets perifused in the presence of 2-cyclohexene-1-one (CHX; 1.0 mM), the secretory response to either D-glucose or 2-ketoisocaproate, but not that evoked by the association of L-leucine and L-glutamine, was severely decreased. This coincided with a decreased stimulation of [45Ca] efflux from prelabelled islets, whereas the inhibitory action of D-glucose or 2-ketoisocaproate upon both [86Rb] and [45Ca] efflux appeared little or not affected. In the presence of D-glucose, the islets exposed to CHX were virtually unresponsive to either forskolin, theophylline or cytochalasin B. A severe decrease in the secretory response to forskolin was also observed in CHX-treated islets exposed to L-leucine and L-glutamine. Except for a somewhat lower sensitivity to NaF, no major change in adenylate cyclase activity or cyclic AMP production was observed in CHX-treated islets. The activity of protein kinase A was decreased in such islets but its responsiveness to cyclic AMP appeared unaltered. Transglutaminase activity was severely decreased in homogenates derived from CHX-treated islets. These findings suggest that CHX, possibly by lowering the GSH content of islet cells, impairs the functional capacity of the effector system for insulin release, in addition to and independently of any effect that it may exert upon nutrient catabolism and cationic fluxes in the islet cells.
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PMID:The coupling of metabolic to secretory events in pancreatic islets: inhibition by 2-cyclohexene-1-one of the secretory response to cyclic AMP and cytochalasin B. 287 68

The activity of adenylate cyclase, its responsiveness to NaF and forskolin, the activity of the protein kinases A and C, and the oxidation of exogenous D-glucose, L-leucine, and L-glutamine were all higher in pancreatic islets removed from lactating, as distinct from nonlactating, rats. Yet, the release of insulin evoked by D-glucose or the association of L-leucine and L-glutamine was lower in the islets obtained from lactating animals. The lactation-induced decrease in secretory activity was not attributable to a change in the insulin content of the islets, was not corrected by exposure of the islets to theophylline or forskolin, and was also observed in response to stimulation by Ba2+. The rapidly exchangeable islet Ca pool, as estimated from the basal value for 45Ca net uptake, was severely decreased in lactation. Moreover, a hypoglycemic sulfonylurea, which stimulated islet 45Ca net uptake much more markedly in lactating than nonlactating animals, provoked, in association with 12-O-tetradecanoylphorbol-13-acetate, a greater insulin output in lactating than nonlactating rats. It is speculated that the decreased secretory activity in islets removed from lactating rats may be accounted for, in part at least, by a decreased Ca content of the islet cells.
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PMID:Influence of lactation upon pancreatic islet function. 300 61

Above a threshold value in excess of 5.6 mM, D-glucose increases the amount of cyclic AMP measured by radioimmunoassay in pancreatic rat islets and their surrounding incubation medium. As judged from the cyclic AMP content of islets exposed to isobutylmethylxanthine (1.0 mM), the glucose-induced increment in the rate of cyclic AMP generation represents a rapid and sustained phenomenon. The stimulant action of glucose on cyclic AMP accumulation is mimicked by L-leucine, and L-glutamine, these amino acids acting synergistically of one another. Trifluoperazine slightly decreases but fails to abolish the effect of glucose. In the absence of extracellular Ca2+, however, the cyclic AMP response to D-glucose, L-leucine and/or L-glutamine is severely impaired. These findings are compatible with the view that an increase in the generation rate of cyclic AMP participates in the process of nutrient-stimulated insulin release. This increase could be secondary to the nutrient-induced accumulation of Ca2+ in the islet cells leading to activation of adenylate cyclase by calmodulin.
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PMID:The stimulus-secretion coupling of glucose-induced insulin release. LIII. Calcium-dependency of the cyclic AMP response to nutrient secretagogues. 618 92

Forskolin activated adenylate cyclase in rat islet homogenates and stimulated cAMP production in intact islets incubated in the absence or presence of either D-glucose or Ca2+. Forskolin failed to affect D-[U-14C]glucose oxidation, glucose-stimulated net 45Ca uptake, or basal insulin release, but enhanced insulin secretion evoked by either nutrients (D-glucose, 2-ketoisocaproate, L-leucine alone or in combination with L-glutamine), or nonnutrient secretagogues (12-O-tetradecanoylphorbol-13-acetate, Ba2+ alone or in combination with theophylline). Forskolin stimulated insulin release from islets incubated in the presence of glucose but in the absence of Ca2+. These findings confirm that a marked increase in cAMP production is not sufficient to cause sustained insulin release. They also suggest that the enhancing action of endogenous cAMP upon insulin release does not depend on a facilitation of Ca2+ influx into islet cells.
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PMID:Forskolin-induced activation of adenylate cyclase, cyclic adenosine monophosphate production and insulin release in rat pancreatic islets. 620 17

Insulin release from pancreata of human fetuses aged 4 to 9 months and from adult pancreata were studied in monolayer cell culture by static incubation and perifusion technique. Fetal pancreata at the midterm of gestation (4 to 6 months) showed no response of insulin release to glucose. In a case of 9 months-old fetus, in which a small but significant increase of insulin release was observed with glucose (300 mg/ml). Tolbutamide (100 microgram/ml) had no effect on insulin release from all the pancreata of fetuses tested. Caffeine (5 and 10 mM), a phosphodiesterase inhibitor, potentiated insulin release by itself and also induced the glucose-stimulated insulin release from the fetal pancreata in the dose related manner. Glucagon (2 microgram/ml), L-isoproterenol (2 microgram/ml), L-arginine (10 mM) and L-leucine (10 mM) failed to induce any increase of insulin release from fetal pancreata. In the presence of caffeine, the significant increase of insulin release from fetal pancreata was observed with L-leucine, but not with L-arginine. There was no evidence of the maturation of B-cells during the culture periods (4 to 8 days), probably lacking the key steps of stimulus-secretion couplings in relation to adenylate cyclase-cyclic AMP system. By contrast, glucose (100 and 300 mg/100 ml), tolbutamide (100 microgram/ml), L-arginine (10 mM) and caffeine (5 mM) caused a significant increase of insulin release from adult pancreata. Thus, the development of human pancreatic B-cells seems to depend substantially on gestational age, being ready to equip most machinary of insulin release before delivery.
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PMID:Monolayer culture of human fetal and adult pancreas. Static and dynamic studies of insulin release in vitro. 699 62

The present study was undertaken to determine whether there are Ca2+ -dependent and -independent pathways of glucose-induced insulin secretion from the pancreatic beta cell line MIN6. Glucose at a concentration of 16.7 mmol/l caused marked increases in cellular free calcium ([Ca2+]i) and insulin secretion, which depended on glucose metabolism. When cells were pretreated with 20 mmol/l mannoheptulose, an inhibitor of glucokinase, the 16.7 mmol/l glucose induced a rise in [Ca2+]i and insulin secretion disappeared. Also, L-leucine and L-arginine increased [Ca2+]i and induced insulin secretion. Under Ca2+ -free conditions, insulin release was still induced, without any change in [Ca2+]i, by these three different stimulants. The cumulative values of insulin secretion were 13.7-29.3% of the control, which were significantly less than that in the presence of Ca2+. Cellular alkalinization occurred in response to all these stimulants, irrespective of the presence of Ca2+. Forskolin, a diterpene activator of adenylate cyclase, produced insulin secretion independently of [Ca2+]i, which accompanied cellular alkalinization. Also, a high glucose level increased cellular cyclic AMP (cAMP) production in the presence and absence of Ca2+, and the effect was diminished by approximately 73% in Ca2+ -free conditions. These results indicate that a high glucose level stimulates both Ca2+ -dependent and -independent insulin secretion from pancreatic beta cells. We suggest that the cAMP production and the cellular alkalinization participate in the Ca2+ -independent mechanism. Spermatogonial proliferation is under the control of FSH, whereas the survival of germ cells is dependent on Sertoli cell function. The observed rise in the number of mitotically inactive Ad-spermatogonia can be explained by a transformation of Ap-spermatogonia into resting Ad-spermatogonia.
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PMID:Glucose induces calcium-dependent and calcium-independent insulin secretion from the pancreatic beta cell line MIN6. 765 49

Cardiopulmonary bypass (CPB) is often followed by pulmonary hypertension, but the effects of extracorporeal circulation on vascular reactivity remain largely unknown. In this study, the influence of total CPB (t-CPB) on beta-adrenergic and cholinergic receptor-mediated pulmonary microvascular responses was examined. Sheep were placed on t-CPB without ventilation. After 90 min, sheep were separated from t-CPB and the lungs were perfused normally for 60 min. Pulmonary artery infusion of acetylcholine (muscarinic cholinergic agonist, ACh) increased pulmonary vascular resistance significantly more and isoproterenol (beta-adrenergic agonist, Iso) decreased pulmonary vascular resistance less after than before t-CPB. The response to sodium nitroprusside (SNP, guanylate cyclase activator) was similar before and after t-CPB. Relaxations (in vitro) of isolated pressurized (20 mmHg) microvessels to Iso and ACh were markedly reduced after t-CPB. Treatment with NPC-15669 (N-[9H-(2,7,-dimethylfluorenyl-9-methoxy)carbonyl]-L-leucine) did not affect these changes in vessel reactivity, although leukocyte sequestration in the lungs was reduced with the drug. The in vitro response to forskolin (adenylate cyclase activator) and SNP was similar before and after t-CPB. Complement-activated serum caused microvessels to contract in response to ACh, but it had no effect on Iso, forskolin, or SNP responses, suggesting that activation of the alternate complement pathway causes a selective reduction in endothelium-dependent relaxation. We conclude that t-CPB impairs cholinergic and beta-adrenergic pulmonary vascular responses due to effects at the level of the transmembrane receptor or coupling to the second messenger systems.
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PMID:Altered beta-adrenergic and cholinergic pulmonary vascular responses after total cardiopulmonary bypass. 884 66