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

The effect of chronic treatment with a long-acting glucagon preparation on liver glucagon and insulin receptors, adenylate cyclase and plasma lipids has been examined in Zucker fatty rats (fa/fa) and their lean littermates (Fa/-). Liver insulin and glucagon receptors were examined using radioreceptor assay techniques. Neither fatty nor lean rats showed any change in insulin receptors after glucagon treatment. Glucagon receptors of the fatty rats showed a 33% drop in the number of the glucagon receptors after glucagon treatment, whilst there was no such change in the lean group. Plasma membranes of the treated fatty rats and their controls bound only 50% as much insulin per mg of liver membrane protein as those of the treated lean rats and their controls. Glucagon treatment raised plasma NEFA in lean rats and reduced them in fatty ones. Plasma cholesterol levels were reduced in both groups of animals as were plasma triglycerides, though to a lesser degree in fatty than in lean animals. Glucagon treatment increased basal and stimulated adenylate cyclase activity in the lean rats and even more so in the fatty ones. The data lend no support to the concept that hypertriglyceridaemia in fatty Zucker rats is a consequence of abnormal glucagon responsiveness.
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PMID:The effect of induced hyperglucagonaemia on the Zucker fatty rat. 20 3

Muscle and blood metabolites, plasma insulin and cyclic adenosine 3',5'-monophosphate (cAMP) levels were investigated in five male runners before and after strenuous intermittent running exercise of short duration. Immediately after the exercise, the mean muscle creatine phosphate level (CrP) had fallen by 74% (P less than 0.02) and 30 min later the initial level was regained in only one subject. Other immediate results were increases in mean muscle lactate (460%, P less than 0.005), glucose (130%), glucose-6-phosphate (G6P, 320%) and fructose-1,6-diphosphate (FDP, 32%). Muscle ATP and glycogen concentration had decreased by 31 and 23% (P less than 0.05), respectively. However, ATP, glucose, G6P and FDP changes were not significant owing to the great individual variation. This may have been due to the different training programmes of the runners. Immediately after the exercise mean plasma insulin was 210% (P less than 0.01), blood glucose 71% (P less than 0.005) and plasma cAMP concentration 260% (P less than 0.01) higher than the pre-exercise values. After running urinary excretion of cAMP was 29% higher than before the exercise. It is concluded that exhaustive, short-term exercise activates the liver adenylate cyclase system so giving rise to an increased level of blood glucose, which is an important source of energy during this type of exercise.
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PMID:Muscle metabolism during and after strenuous intermittent running. 21 Apr 97

The influence of portal blood factors on canine liver regeneration was studied with graded nonhepatic splanchnic evisceration, coupled with 44 and 72 per cent hepatectomies. In one type of experiment, the pancreas was retained while the rest of the intra-abdominal gastrointestinal tract was removed. In a second variety, total pancreatectomy was performed with preservation of the intra-abdominal organs. In a third kind of experiment, total nonhepatic splanchnic evisceration was performed. Liver regeneration after hepatectomy was decreased by all three kinds of viscera removed as judged by deoxyribonucleic acid synthesis, autoradiography and mitotic index. Pancreatectomy and nonpancreatic splanchnic evisceration caused almost equal decreases in the regenerative response. Total nonhepatic splanchnic evisceration essentially halted regeneration during the first three postoperative days and intraportal infusions of insulin or glucagon, or both together, did not reverse this effect. The decrease in liver membrane bound adenyl cyclase activity and biphasic change in liver cyclic 3', 5' -adenosine monophosphate concentrations normally seen after partial hepatectomy were disrupted after the various eviscerations. Adenyl cyclase activity and cyclic 3', 5' -adenosine monophosphate concentrations tended to be higher than normal in the eviscerated dogs. These observations provide more support for our previously proposed hypothesis that control of liver regeneration is by multiple factors. Pancreatic hormones are important modifiers of this response but, by no means, exercise exclusive control. Other substances of gastrointestinal origin, presumably including hormones and nutrient supply apparently play important specific roles. The volume of portal flow is a secondary and nonspecific, but possibly significant, factor.
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PMID:The effect of splanchnic viscera removal upon canine liver regeneration. 21 May 29

Glucagon was tested for its effect on plasma adenosine 3',5'-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation.
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PMID:Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis. 21 45

Insulin secretion was stimulated and cyclic adenosine 3', 5'-monophosphate (cAMP) levels were elevated in isolated rat islets by 27.5 mmol/l glucose. Alloxan caused a dose-dependent decrease in both variables with complete obliteration of insulin release at a concentration of 1.25 mmol/l. D-glucose, in the presence or absence of extracellular calcium, or 3-0-methyl-D-glucose (both at 27.5 mmol/l) protected completely against the effects of alloxan on both glucose-induced insulin release and cAMP Levels. 3-0-Methylglucose did not stimulate insulin secretion or elevate cAMP and did not interfere with glucose-stimulated secretion or elevation of cAMP. When glucose-stimulated insulin release was abolished by alloxan, the metabolism of glucose, determined by the rate of 3H2O formation from [5-3H] glucose, was depressed by 20%. It is concluded that alloxan altered the adenylate cyclase system such that it could no longer be stimulated by glucose. Glucose-stimulated insulin secretion or elevation of cAMP did not appear essential for glucose to protect against alloxan. Protection by 3-0-methylglucose did not appear to be mediated through an alteration of cAMP metabolism. Alloxan did not inhibit glucose-induced insulin secretion by grossly altering glycolysis.
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PMID:Effects of alloxan on glucose-stimulated insulin secretion, glucose metabolism, and cyclic adenosine 3', 5'-monophosphate levels in rat isolated islets of langerhans. 21 80

C-AMP causes release of growth hormone from the pituitary. Prostaglandin increases pituitary adenylate cyclase and C-AMP and therefore acts like a growth hormone-releasing hormone. Using PGE2 (30 microgram per kilo body weight) given intravenously we have demonstrated that in no case was there a growth hormone response to insulin hypoglycaemia when PGE2 failed to evoke a response. However in 6 of 18 patients unresponsive to insulin hypoglycaemia a significant rise in growth hormone was obtained from PGE2. We argue that in these 6 patients hypothalamic unresponsiveness to hypoglycaemia must be operative whereas PGE2 acting directly at pituitary level is likely to have caused the release of preformed growth hormone from the pituitary. Administration of PGE2 does not cause hypoglycaemia but rather a slight rise in the plasma glucose level. Thus the risk of brain damage which is inherent in the insulin hypoglycaemia test is avoided.
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PMID:Growth hormone response to prostaglandin E2. 21 33

Previously, we have shown that preparations of hCG bind to bovine thyroid membranes, as judged from their ability both to inhibit the binding of 125I-labeled bovine TSH (bTSH) and to activate adenylate cyclase (Amir, S.M., H. Uchimura, and S.H. Ingbar, J Clin Endocrinol Metab 45: 280, 1977). In the present studies, 125I-labeled, highly purified bTSH ([125I]bTSH) has been shown to bind specifically and saturably to receptors in a particulate fraction from rat testis. At 37 C, binding was rapid, reaching a maximum level in less than 15 min, but then declining markedly during the next several hours. At 22 C, binding reached a steady state after 2 h and remained unchanged for another 22 h. Binding of [125I]bTSH was greatest at pH 5.5, at which pH more than 50% of [125I]bTSH was bound in the presence of 330 microgram/ml particulate protein, the concentration of protein that yielded maximum binding. Nevertheless, the majority of experiments were conducted at lesser protein concentrations and at physiological pH (7.45), under which conditions total binding was only 25% of that measured at pH 5.5. Scatchard plots indicated the presence of a single binding site with a dissociation constant of 5.8 X 10(-8) M and a binding capacity of 0.22 nmol/mg protein on the basis of data obtained at 22 C and pH 7.45. Both crude and highly purified preparations of hCG inhibited the binding of [125I]bTSH to testis particulate fraction; crude hCG had 46 times the activity, and purified hCG had only one-tenth the activity of bTSH itself in this respect. This was true despite the fact that with respect to the displacement of [125I]hCG, crude and purified hCG were almost equally active. Bovine LH had one-third the activity of bTSH in displacing [125I]bTSH. Human FSH inhibited [125I]bTSH binding only slightly at the highest concentration tested, while glucagon, insulin, PRL, and GH were inactive. Purified bTSH inhibited the binding of [125I]hCG to testis particulate fraction but contained only about 2% of the activity of purified hCG. Lineweaver-Burk analysis suggested that inhibition of [125I]hCG binding by bTSH was competitive in nature. Purified bTSH stimulated cAMP production in Leydig cells, but with only about 0.1% of the activity of purified hCG. It is concluded that bTSH binds reversibly, saturably, and with relatively high affinity to receptors in rat testis that are either the same as receptors for hCG and LH or that interact therewith. bTSH, like hCG, is capable of stimulating the production of cAMP in rat Leydig cells, but is much less potent than hCG in this regard. Preparations of crude hCG contain a factor lacking hCG activity in bioassay, immunoassay, and receptor assay that is especially potent in displacing [125I]bTSH from receptors in testis, as has earlier been described for bTSH receptors in bovine thyroid membranes.
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PMID:Binding of bovine thyrotropin to receptors in rat testis and its interaction with gonadotropins. 21 36

Incubation of pancreatic islets of fed rats at glucose 10 and 15 mM induced a rapid rise of the islet cyclic adenosine 3',5'-monophosphate (cAMP) content. Maximum levels were attained at 15 min and lasted until 30 min, after which cAMP declined again. Insulin secretion increased most rapidly from 15 min onward, i.e. after the rapid rise of cAMP. Islet cAMP at either 15 or 30 min showed its major concentration-dependent increase between glucose 7.5 and 10 mM. Glucose 15 mM did not further enhance the cAMP response, although this concentration increased insulin secretion more than two-fold over values observed at glucose 10 mM. Thus, the glucose dose-response relations for cAMP levels and insulin secretion appear to be different, indicating that factors other than cAMP alone determine the secretory response to glucose. Fasting for 24 and 72 h progressively inhibited glucose-induced insulin secretion. At glucose 15 mM the secretory inhibition disappeared after 30-45 min, but at glucose 10 mM it persisted for at least 90 min. Increasing periods of fasting also progressively delayed and inhibited the cAMP response to glucose, most strongly at glucose 10 mM. Fasting for 24 h shifted the glucose dose-response curves for cAMP and insulin secretion to the right, but the maximum responses at glucose 37.5 mM were not significantly inhibited. The secretory inhibition appeared to be linearly related with the cAMP content in two different ways: (a) At fixed concentrations of glucose, the increasing of the cAMP response (at 15 min) as induced by 24 and 72 h of fasting correlated with the secretory inhibition over the initial 30 min. (b) At one fixed period of fasting (24 h), the variable percent inhibition of the cAMP response to graded concentrations of glucose (5-37.5 mM) correlated with the percent secretory inhibition at these concentrations. These correlations were no longer apparent after 30 min of incubation. The results support the view that inhibition of the adenylate cyclase-cAMP system is a major determinant factor in fasting-induced impairment of insulin secretion during the initial 30 min of glucose stimulation.
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PMID:Insulin secretion and cyclic adenosine 3', 5'-monophosphate levels in pancreatic islets of fed and fasted rats. Time course and dose kinetics during glucose stimulation. 21 91

Islets of Langerhans, isolated from normal or 19-day pregnant rats, were cultured for 20 h at 37 degrees C in tissue culture medium 199. When islets were cultured in medium containing low glucose (5.5 mM), the higher adenylate cyclase activity and insulin secretory responses characteristic of islets from pregnant rats were maintained during the test period of 29 h. Islets from normal and pregnant rats were also cultured for 20 h in medium containing a very high glucose concentration (83.3 mM) in order to load the B cells with glycogen. It was found, after glycogen loading, that, while adenylate cyclase activity increased to a greater extent in islets from pregnant rats than controls, this activity was not increased in proportion to the striking changes in insulin release rate observed in pregnant rat islets. The results show that the difference in insulin secretory response between islets from normal and pregnant rats may be preserved when the islets are cultured for 20 h, and that these differences are enhanced for a variety of reasons after culture of islets in 83.3 mM glucose.
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PMID:Preservation of the effects of pregnancy on rat islets of Langerhans in tissue culture. 21 79

Adipose-tissue triacylglycerol is the major energy store in man. The physiological importance and biochemical mechanism of the hormonal control of lipolysis in white adipose tissue is reviewed. Rates of lipolysis and fatty acid release observed when adipose tissue is incubated in vitro are compared with rates of triacylglycerol turnover in man. It appears that enhanced rates of lipolysis in vivo, for example during fasting and exercise, may be a substantial fraction of the maximum obtainable by hormone stimulation in vitro. There is considerable species variation in the hormonal sensitivity of adipose tissue. Some hormones that stimulate lipolysis in vitro may not be significant lipolytic agents at physiological concentrations in vivo. In man and rat, the most important acutely acting lipolytic and anti-lipolytic hormones are catecholamines and insulin respectively. The sympathetic nervous system may play a role at least as important as circulating catecholamines in the mobilization of stored triacylglycerol. The effects of acute lipolytic hormones are modulated in the long term by corticosteroids and thyroid hormone. Stimulation of lipolysis is believed to be mediated by the increased intracellular cyclic AMP concentration that occurs after interaction of hormones with specific receptors in the plasma membrane. The properties of membrane receptors, adenylate cyclase, cyclic AMP phosphodiesterase, cyclic AMP-dependent protein kinase and triacylglycerol lipase, as studied in rat and human adipose tissue, are discussed. Several features of the action of lipolytic hormones in vitro are difficult to account for by the hypothesis that cyclic AMP is the only "second messenger" regulating lipase activity. These include anomalous effects of hormones at high concentrations and the possible existence of feedback inhibition limiting the accumulation of cyclic AMP and the stimulation of lipolysis. The mechanism of the anti-lipolytic action of insulin is at present unknown.
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PMID:Hormonal control of adipose-tissue lipolysis. 21 67


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