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

5'-Guanylylimidodiphosphate (Gpp(NH)-p) stimulates adenylate cyclase [ATP-pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in plasma membranes isolated from frog and salmon erythrocytes, from rat adrenal, hepatic, and fat cells, and from bovine thyroid cells. The nucleotide acts cooperatively with the various hormones (glucagon, secretin, ACTH, thyrotropin, and catecholamines) that stimulate these adenylate cyclase systems with resultant activities that equal or exceed those obtained with hormone plus GTP or with fluoride ion. In the absence of hormones, Gpp(NH)p is a considerably more effective activator than GTP, and, under certain conditions of incubation, stimulates rat fat cell adenylate cyclase to levels of activity (about 20 nmoles of 3',5'-adenosine monophosphate mg protein per min) far higher than reported hitherto for any adenylate cyclase system examined. The nucleotide activates frog erythrocyte adenylate cyclase when the catecholamine receptor is blocked by the competitive antagonist, propranolol, and activates the enzyme from an adrenal tumor cell line which lacks functional ACTH receptors. In contrast, Gpp(NH)p does not stimulate adenylate cyclase in extracts from Escherichia coli B. Gpp(NH)p appears to be a useful probe for investigating the mechanism of hormone and nucleotide action on adenylate cyclase systems in eukaryotic cells.
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PMID:5'-Guanylylimidodiphosphate, a potent activator of adenylate cyclase systems in eukaryotic cells. 460 68

We have shown that two unrelated prostaglandin antagonists block both thyrotropin (TSH) and prostaglandins E (PGE(1), PGE(2)) stimulation of thyroidal adenyl cyclase activation and cyclic 3',5'-adenosine monophosphate (cAMP) formation, suggesting that prostaglandins play an important role in regulating thyroid function. To further explore this postulate, we measured prostaglandin content by radioimmunoassay in homogeneous bovine thyroid cell preparations in the presence and absence of TSH. Antibodies to albumin-conjugated PGE(1) and PGF(2alpha) showed specificity for prostaglandins E and F, respectively, but reacted, albeit far less effectively, with heterologous prostaglandins. A double antibody system was used to separate free from antibody-bound PGE(1)-(3)H and PGF(2alpha)-(3)H. Thyroid cells were extracted with ethanol/ethyl acetate and the various prostaglandins separated on silicic acid columns. Recoveries of added PGE(1)-(3)H and PGF(2alpha)-(3)H through the extraction and separation procedures ranged from 50-80%. The sensitivity of the method was 10-50 pg. Basal thyroid cell content of PGE(1) and PGF(2alpha) "equivalents" varied between cell preparations (range = 2-6 ng/0.2 ml cell suspension) but, in each instance, remained constant during 5-30-min incubations at 37 degrees C. TSH, 10-100 mU/ml, increased the levels of cell PGE(1) and PGF(2alpha) "equivalents" 30-80% above basal during 5-15-min incubations. The stimulatory effect was specific for TSH, no increase in PGE(1) or PGF(2alpha) "equivalent" levels being seen with luteinizing hormone (LH), human growth hormone (HGH), adrenocorticotropic hormone (ACTH), or glucagon. These data support the thesis that prostaglandins may mediate TSH effects on thyroid.
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PMID:Thyrotropin increases prostaglandin levels in isolated thyroid cells. 462 70

The effects of ingested and infused glucose upon circulating glucagon-like immunoreactivity (GLI) were compared in 14 triply catheterized conscious dogs. Within 60 min after the intraduodenal administration of 2 g/kg of glucose, the mean level of glucagon-like immunoreactivity in the vena caval plasma more than doubled, whereas after intravenous infusion of the same dose over a 90 min period no change in the mean vena caval level was observed; during glucose infusion mean glucagon-like immunoreactivity in the pancreatic venous effluent declined, suggesting that hyperglycemia suppresses rather than stimulates pancreatic glucagon secretion. To determine if the rise in glucagon-like immunoreactivity that occurs during glucose absorption was of pancreatic origin, the effect of pancreatectomy performed 1 hr after the intraduodenal administration of glucose was determined. Although circulating insulin disappeared after resection of the pancreas, the level of glucagon-like immunoreactivity continued to rise, establishing its extrapancreatic origin. In other experiments, measurements of Glucagon-like immunoreactivity in plasma obtained simultaneously from pancreaticoduodenal and mesenteric veins and from the vena cava revealed the increment after intraduodenal glucose loading to be greatest in the mesenteric vein in 8 of 12 experiments, favoring the gut as the likely source of the rise. To characterize gut glucagon-like immunoreactivity, acid-alcohol extracts of canine jejunum were compared with similar glucagon-containing extracts of canine pancreas with respect to certain physical and biological properties. On a G-25 Sephadex column the elution volume of the jejunal immunoreactivity was found to be smaller than that of glucagon, which suggested a molecular size at least twice that of pancreatic glucagon. Furthermore, the in vivo and in vitro biological activities of the eluates containing jejunal glucagon-like immunoreactivity appeared to differ from those of eluates containing pancreatic glucagon. The jejunal material lacked hyperglycemic activity when injected endoportally into dogs, was devoid of glycogenolytic activity in the isolated perfused rat liver, and did not increase hepatic 3',5' cyclic adenylate in the perfused liver; however, like glucagon it appeared to stimulate insulin release. It seems quite clear the material in intestinal extracts either is a different substance or a different form from that of true pancreatic glucagon, although it crossreacts in the radioimmunoassay with antibodies to glucagon. It is concluded, (a) that hyperglycemia does not stimulate and probably suppresses the secretion of pancreatic glucagon; (b) that during intestinal absorption of glucose, a rise in glucagon-like immunoreactivity occurs; (c) this immunoreactivity is derived from an extrapancreatic site, probably the gut; (d) that the glucagon-like immunoreactivity extractable from jejunum is not the same as pancreatic glucagon but is a larger molecule devoid of hyperglycemic and glycogenolytic activity, a cross-reactant in radioimmunoassay for glucagon; and (e) that the eluate in which jejunal immunoreactivity is contained can stimulate insulin release in conscious dogs.
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PMID:Characterization of the responses of circulating glucagon-like immunoreactivity to intraduodenal and intravenous administration of glucose. 563 20

Effects of various alpha adrenergic agents on insulin release and cyclic 3':5'-adenosine monophosphate (cAMP) accumulation in pancreatic islets were investigated. Clonidine, epinephrine, alpha-methylnorepinephrine and norepinephrine were most potent and methoxamine and phenylephrine least potent in inhibiting the glucose-stimulated insulin release. Yohimbine and phentolamine were the most effective and prazosin was the least effective in antagonizing the epinephrine-inhibited insulin release. Clonidine markedly inhibited the glucagon-stimulated cAMP accumulation, whereas methoxamine showed weak inhibition. Yohimbine markedly increased cAMP accumulation in the presence of epinephrine, whereas prazosin showed little effect. The effects of alpha adrenergic agents on rabbit aorta contraction were also examined for comparison with alpha adrenergic receptors in pancreatic islets. In the aorta, the order of agonist potency was norepinephrine greater than phenylephrine greater than epinephrine greater than methoxamine greater than alpha-methylnorepinephrine and that of antagonist potency was prazosin greater than WB-4101 greater than phentolamine greater than dihydroergotamine greater than phenoxybenzamine greater than yohimbine. These orders of potencies were markedly different from those in pancreatic islets. These results clearly demonstrate that the alpha adrenergic receptors in rat pancreatic islets are different from those on rabbit aorta (alpha-1) and are typical postsynaptic alpha-2 adrenergic receptors.
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PMID:Postsynaptic alpha-2 adrenergic receptors in isolated rat islets of Langerhans: inhibition of insulin release and cyclic 3':5'-adenosine monophosphate accumulation. 611 Jul 70

Short-lasting hypothermia during thiobutabarbital general anaesthesia causes no decrease of the absolute ATP level in the blood and liver of rats. The adenylate energy charge in the tissues is relatively high - 0.86 in the liver and 0.85 in the muscles, which might be an evidence of a significant "energy sparing" during moderate hypothermia (26 +/- 1 degree C). Somatostatin in a dose of 20 micrograms/kg of body weight given to the rats during hypothermia decreased the ATP level, the ATP/ADP ratio and the adenylate energy charge in the studied tissues, especially in the liver, evidencing increased intensity of catabolic processes caused by the inhibitory action of somatostatin on the release of insulin and glucagon, among other hormones, and on the change of the insulin/glucagon ratio.
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PMID:Somatostatin effect on the level of adenyl nucleotides in the blood and tissues of rats during short-lasting hypothermia. 614 95

A novel adenylate cyclase activity was found in crude homogenates of Neurospora crassa. The adenylate cyclase had substantial activity with ATP-Mg2+ as substrate differing significantly from the strictly ATP-Mn2+-dependent enzyme characterized previously. Additionally, the ATP-Mg2+-dependent activity was stimulated two- to fourfold by GTP or guanyl-5'-yl-imido-diphosphate (Gpp(NH)p). We propose that the ATP-Mg2+-dependent, guanine nucleotide-stimulated activity is due to a labile regulatory component (G component) of the adenylate cyclase which was present in carefully prepared extracts. The adenylate cyclase had a pH optimum of 5.8 and both the catalytic and G component were particulate. The Km for ATP-Mg2+ was 2.2 mM in the presence of 4.5 mM excess Mg2+. Low Mn2+ concentrations had no effect on adenylate cyclase activity whereas high concentrations of Mn2+ or Mg2+ stimulated the enzyme. Maximal Gpp(NH)p stimulation required preincubation of the enzyme in the presence of the guanine nucleotide and the K1/2 for Gpp(NH)p stimulation was 110 nM. Neither fluoride nor any of a variety of glycolytic intermediates or hormones, including glucagon, epinephrine, and dopamine, had an effect on ATP-Mg2+-dependent adenylate cyclase activity. However, the enzymatic activity was stimulated not only by GTP but also by 5'-AMP and was inhibited by NADH.
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PMID:Characterization of an ATP-Mg2+-dependent guanine nucleotide-stimulated adenylate cyclase from Neurospora crassa. 621 25

Responses to glucagon from the adenylate cyclasecyclic adenosine monophosphate (cAMP) system in liver slices from control and streptozotocin-induced diabetic rats were compared. Tissue cAMP levels were similar in the basal state but responded poorly to glucagon (20 pg/ml-2 microgram/ml) in diabetic rats. Insulin treatment of diabetic rats in vivo led to a reversal of the glucagon stimulation towards the values in the control rats. The basal and glucagon-stimulated activities of adenylate cyclase in crude membrane fractions were similar in both groups. Plasma immunoreactive glucagon levels in diabetic rats were approximately three times higher than those in normal rats. Liver slices obtained from normal rats, which were injected with glucagon (0.2 mg, i.m.) 45 min previously, also showed an impaired responsiveness to glucagon of tissue cAMP levels, while no significant difference in adenylate cyclase activity was observed between the normal and glucagon-treated rats. These results suggest that the responsiveness of liver slices from the streptozotocin-induced diabetic rat has been modified by the preceding hyperglucagonemia. The reason for the observed differences between slices and crude membranes is not known.
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PMID:A decreased response of cyclic adenosine monophosphate concentrations to glucagon in liver slices from streptozotocin-induced diabetic rats. 624 31

Spontaneously transformed RL-PR-C rat hepatocytes, unlike their normal differentiated progenitor cells, are insensitive to glucagon, although seemingly possessing large numbers of glucagon receptors and although retaining guanyl nucleotide regulatory protein-adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] system that responds to catecholamines, cholera toxin, and fluoride ions. Biochemical fusions between normal RL-PR-C hepatocytes or purified rat liver plasma membranes (whose adenylate cyclases were previously irreversibly inactivated with N-ethylmaleimide) with spontaneously transformed hepatocytes produced hybrids whose basal and fluoride-stimulated adenylate cyclase activities reflected those of the parental transformed cells but that now responded to glucagon. Using cholera toxin-catalyzed ADP-riboxylation of transformed hepatocytes to mark their guanyl nucleotide regulatory protein, fusiong such cells with N-ethylmaleimide-treated normal hepatocytes, and examining glucagon stimulation of adenylate cyclase activity in fusion hybrids produced results suggesting that the regulatory protein of the transformed cells is functionally normal. In fusion experiments between N-ethylmaleimide-treated hepatocytes and igeon erythrocytes, we found that normal, but not transformed, hepatocytes were effective in conferring glucagon sensitivity upon erythrocytes. Glucagon binding data revealed that, whereas normal RL-PR-C hepatocytes have two independent classes of binding sites, one of higher and the other of lower affinity, transformed cells possess only the low-affinity receptors. From these and previous observations, it is possible to conclude that the insensitivity of spontaneously transformed RL-PR-C hepatocytes to glucagon is due to the loss, during the transformation process, of the high-affinity glucagon receptor.
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PMID:Restoration of glucagon responsiveness in spontaneously transformed rat hepatocytes (RL-PR-C) by fusion with normal progenitor cells and rat liver plasma membranes. 626 32

The ability of glucagon to induce a state of desensitization to glucagon responsiveness has been examined in a cloned line of normal, differentiated, diploid rat hepatocytes (RL-PR-C). These cells, which respond to glucagon with increased production of cyclic AMP, become refractory to further stimulation of cyclic AMP synthesis following a 4 hour exposure period of the cells to the hormone. Refractoriness to glucagon was demonstrated over a wide range of hormone concentrations (10(-12) to 10(-6) M). In desensitized cells that were subsequently washed free of the hormone, recovery from refractoriness was complete by 20 hours. The mechanism underlying this desensitization does not appear to involve decreased receptor numbers, increased efflux of cyclic AMP from the cells, increased degradation of cyclic AMP by phosphodiesterase, or an alteration in the catalytic unit of the adenylate cellular cyclic AMP responsiveness to glucagon in normal RL-PR-C hepatocytes may involve glucagon a reversible uncoupling of glucagon receptors from adenylate cyclase. In addition, late passage, spontaneously transformed RL-PR-C hepatocytes were found to exist in a state in which glucagon receptors are permanently uncoupled from adenylate cyclase.
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PMID:Uncoupling of the glucagon receptor-adenylate cyclase system by glucagon in cloned differentiated rat hepatocytes. 627 54

Hepatocytes isolated from the livers of starved, sham-operated, bilaterally nephrectomised and ureter-ligated rats as well as rats with ischaemic acute renal failure were used for a comparative study of the effects of different hormones on gluconeogenesis. In all tested groups dibutyryl-3':5'-adenosine monophosphate inhibits glucose synthesis from pyruvate whereas this process is not affected by glucagon and only slightly activated by adrenalin. In contrast, gluconeogenesis from dihydroxyacetone was stimulated by all three hormones at the expense of the conversion of dihydroxyacetone to lactate. In the presence of l-serine adrenalin, glucagon and dibutyryl cAMP also stimulate glucose synthesis, which is more marked in bilaterally nephrectomised and ureter-ligated animals. In half of the experiments with bilaterally nephrectomised rats (group BN 2), lack of sensitivity of hepatocytes to all tested hormones on gluconeogenesis from serine or dihydroxyacetone was observed. The beta-adrenergic antagonist propranolol reduced the stimulatory effect of adrenalin on glucose synthesis from serine and abolished the influence of catecholamines in the presence of dihydroxyacetone and pyruvate. This suggests that both alpha- and beta-receptors are involved in the activation of hepatic gluconeogenesis. Insulin and parathyroid hormone did not change the rate of glucose synthesis in any of the experimental groups.
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PMID:Effect of hormones on hepatocyte gluconeogenesis in different models of acute uraemia. 629 38


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