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)

Medullary thyroid carcinoma (hMTC) cells were established from nine patients with MTC disease to initiate a new approach of adjuvant medical therapy in these patients. We measured calcitonin (CT) secretion, DNA synthesis, and cell proliferation in vitro and their response to various substances. Nerve growth factor (NGF) (0.01 to 10 micrograms/ml), glucagon (0.01 to 100 micrograms/ml), and isoproterenol (4 to 500 micrograms/ml) stimulated CT secretion and DNA synthesis in hMTC cells. Other substances, calcium (1.0 to 15 mmol), pentagastrin (1.0 to 50 mumol), dibutyryl-cyclic-adenosine-monophosphate (1.0 to 100 mumol), and phorbol ester TPA (1.0 to 100 nmol), stimulated CT secretion but not DNA synthesis. In addition, NGF enhanced cell proliferation of hMTC cells 2- to 3- fold and caused an increased sensitivity of these cells for chemotherapy in vitro. Thus 0.5 microgram/ml doxorubicin (half-maximal effective dose) induced a cell death rate of up to 32.8%, which was enhanced by preincubation with NGF to 68.1% (1.0 microgram/ml, NGF) and to 100% (10.0 micrograms/ml, NGF), respectively. Pulsative stimulation of APUD cell carcinomas with NGF may therefore improve the response rate of these tumors to chemotherapy, which would be of significant clinical importance for patients with residual postoperative MTC tissue.
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PMID:Nerve growth factor (NGF) sensitizes human medullary thyroid carcinoma (hMTC) cells for cytostatic therapy in vitro. 368 43

Adenylate cyclase (AC) activity was demonstrated histochemically using adenylate-(beta,gamma-methylene)diphosphate as substrate in cryostat sections of livers from 45 rats treated for 7-10 weeks with N-nitrosomorpholine (NNM) (120 mg/l drinking water) and from nine untreated control rats. The enzyme patterns of normal tissue, preneoplastic and neoplastic lesions were characterized and correlated with the morphologically defined stages of tumour development in the liver. Light microscopically, the enzyme activity of normal tissue was restricted to the plasma membrane, and was most pronounced along the bile canaliculi of the hepatocytes. In glycogen storage foci and mixed cell foci induced by NNM no, or only very weak, AC activity was visible. In the cells of neoplastic nodules and hepatocellular carcinomas AC activity was also clearly reduced. However, in small parts of the plasma membrane which lined lumina resembling normal bile canaliculi and in cytoplasmic vesicles closely associated with these structures, some AC activity was occasionally detected by light and electron microscopy. Whereas the tissue of normal appearance surrounding the lesions showed a marked increase in AC activity in the presence of glucagon, forskolin and cholera toxin. AC activity in the preneoplastic and neoplastic liver lesions could not, or could only weakly, be stimulated by this treatment. As demonstrated in serial sections of the foci, the reduction in AC activity corresponded to changes in the activity of other enzymes studied earlier in the same model. Thus the reduction in AC activity was accompanied by a decrease in the activity of glucose-6-phosphatase and glycogen phosphorylase, and by an increase in the activity of glucose-6-phosphate dehydrogenase. The results support the concept that the focal changes in the activity of many enzymes (including those of carbohydrate metabolism) during hepatocarcinogenesis are the consequence of aberrations in superordinate regulatory mechanisms of cell metabolism.
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PMID:Loss of adenylate cyclase activity in preneoplastic and neoplastic lesions induced in rat liver by N-nitrosomorpholine. 369 88

We investigated by micropuncture the effects of glucagon and parathyroid hormone (PTH) on thin limbs of juxtamedullary nephrons of rats with reduced plasma concentration of endogenous glucagon, PTH, antidiuretic hormone (ADH) and calcitonin, all four hormones enhancing the adenylate-cyclase activity in the thick ascending limbs and the distal nephron. Such a hormonal depletion suppresses the corticomedullary concentration gradient, making favourable conditions for studying the influence of these hormones on the renal concentrating mechanism. Administration of glucagon (4.4 ng/min-1) or PTH (5 mU/min-1) to these hormone-deprived rats elicited the expected decrease in urinary Mg and Ca fractional excretion without modifying either fractional or absolute excretion of water. At the tip of the loop, glucagon enhanced the loop fluid osmolality by 20%, but left the delivery of water unchanged. The Na and Cl concentrations increased significantly with the osmolality, resulting in a positive correlation between the fractional delivery of either ion and the loop fluid osmolality. PTH increased the fraction of filtered phosphate delivered to the thin limbs, as expected, but, in contrast to glucagon, did not alter either the Na, Cl, or total solute fractional deliveries. The Mg, Ca and K deliveries were unaffected by glucagon and PTH. In conclusion, glucagon, which activates the cyclase system of both the medullary and cortical portion of the thick ascending limb, enhances the delivery of salt to the tip of the loop by net sodium chloride addition to the descending limb. PTH which activates the adenyl-cyclase system only in the cortical thick ascending limb cannot enhance such NaCl delivery. NaCl, when added, might therefore originate from the medullary thick ascending limb.
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PMID:Effects of glucagon and PTH on the loop of Henle of rat juxtamedullary nephrons. 371 66

The effects of synthetic human calcitonin (HCT) on water and electrolyte deliveries to the thin limbs of Henle's loop of juxtamedullary nephrons were investigated by micropuncture in the rat. To avoid undesirable interference with exogenous calcitonin, experiments were performed in hormone-deprived rats with reduced circulating calcitonin, antidiuretic hormone, parathyroid hormone and glucagon, all four of which stimulate the adenylate-cyclase activity in the thick ascending limb and the distal tubule. Administration of HCT (1.0 mU/min X 100 g body wt) to such rats significantly reduced the urinary fractional excretion rate of water, Mg, Ca and K. At the tip of the longlooped nephrons, the fractional delivery of water diminished in the presence of HCT, although the glomerular filtration rate of these nephrons was unaltered. Simultaneously, the loop fluid osmolality rose significantly. HCT, however, did not alter the fraction of total filtered solutes remaining in the thin limbs, nor the NaCl fractional delivery. As previously observed in this laboratory with dDAVP, the reduced fractional delivery of water at the hairpin turn was accompanied by a decrease in Mg and Ca deliveries in rats given HCT, indicating that the handling of these two ions along the descending limb may be linked in part to the water movements in this nephron segment. The fractional deliveries of K at the hairpin turn and in urine were significantly correlated, and both decreased in the presence of HCT. Since, as shown previously, HCT reduces the net addition of K along the superficial distal tubule, it is concluded that calcitonin inhibits the medullary recycling of K between the nephron terminal segments and the loop of Henle of juxtamedullary nephrons.
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PMID:Effects of human calcitonin on water and electrolyte movements in rat juxtamedullary nephrons: inhibition of medullary K recycling. 371 48

Halothane, in a number of tissues, alters the activity of adenylate cyclase, the enzyme that catalyzes the formation of cyclic 3',5'-adenosine monophosphate, an important intracellular regulator. The present studies demonstrate that in rat liver whole homogenates, basal and glucagon-stimulated adenylate cyclase activity is increased by halothane. In isolated rat liver membranes, halothane does not increase basal activity and it decreases activity stimulated by glucagon. Suspension of membranes in the cytosol fraction restores the halothane-induced increase of basal and glucagon-stimulated activity. When cytosol denatured by trypsin or heat was used, the halothane-induced increase in glucagon-stimulated activity was lost, but the increase of basal activity was still observed. Suspension of membranes in albumin solution restored the effect of halothane on basal activity only. These results suggest that presence of heat-labile proteins in the cytosol fraction that modulate the halothane interaction with rat liver adenylate cyclase.
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PMID:Effect of halothane on rat liver adenylate cyclase: role of cytosol components. 399 14

Intraperitoneal injections of either cyclic AMP or dibutyryl cyclic AMP are capable of producing a wave of autophagy in rat liver which resembles closely that stimulated by glucagon. These autophagic vacuoles are acid-phosphatase-positive and appear to arise via the envelopment of organelles by double-walled cisterna. At later times these autophagic vacuoles are usually surrounded by a single membrane. Injection of equimolar amounts of 5'-AMP failed to produce a wave of autophagy. These findings constitute preliminary evidence that glucagon-stimulated autophagy is mediated at least in part by cyclic AMP.
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PMID:Studies on cellular autophagocytosis. Cyclic AMP- and dibutyryl cyclic AMP-stimulated autophagy in rat liver. 412 1

Triiodo-L-thyronine (T(3)) added in vitro to fat pads from normal, or propylthiouracil-treated rats enhanced the rate of release of glycerol and free fatty acids (FFA) in the presence of epinephrine. An effect of T(3) was also demonstrated in the presence of adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone, or glucagon in studies with tissue from normal rats. The minimal effective concentration of T(3) was approximately 2.5 x 10(-5) mole/liter for intact fat pads and 3 x 10(-6) mole/liter for fat cells. With fat pads from propylthiouracil-treated rats the effect of T(3) was not apparent until the 3rd hr of incubation. Enhancement of epinephrine-stimulated lipolysis by T(3) was evident during the 1st hr of incubation of fat pads from normal rats, and fat cells responded almost immediately to the presence of T(3). When added alone or in the presence of theophylline, 3',5'-adenosine monophosphate or its dibutyryl derivative, T(3) had little or no effect on lipolysis. The effect of T(3) was observed with or without glucose in the medium, and was not inhibited by cycloheximide or actinomycin D. It did not persist when tissues, after incubation in the presence of T(3) were transferred to medium without T(3). No effect of T(3) on glucose uptake in the presence of epinephrine, ACTH, or insulin was demonstrated.
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PMID:An in vitro effect of triiodothyronine on rat adipose tissue. 429 92

The secretion of calcitonin by slices of porcine thyroid glands has been investigated. Calcitonin in the incubation medium was determined by radioimmunoassay. Secretion of calcitonin was diminished when calcium or magnesium was omitted and was increased stepwise as the concentration of calcium or magnesium in the incubation medium was increased. Calcitonin secretion was augmented substantially when either the quantity of thyroid tissue or volume of incubation medium was increased. Secretion of calcitonin was stimulated by glucagon, theophylline, and dibutyryl cyclic 3',5'-adenosine monophosphate. It is concluded that calcitonin secretion is regulated by the concentration of calcium and magnesium, that secretion may be inhibited by calcitonin or a precursor and that secretion can be stimulated by increasing the concentration of cyclic 3',5'-adenosine monophosphate in the parafollicular cells of the thyroid gland.
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PMID:Effects of glucagon, dibutyryl cyclic 3',5'-adenosine monophosphate, and theophylline on calcitonin secretion in vitro. 431 83

The effects of several prostaglandins (PG) and a highly purified preparation of cholera enterotoxin (CT) on intestinal mucosal adenyl cyclase activity and the effect of CT on intestinal mucosal cyclic 3',5'-adenosine monophosphate concentration were determined in guinea pig and rabbit small intestine and were correlated with the effects of the same agents on ion transport. Adenyl cyclase activity, measured in a crude membrane fraction of the mucosa, was found at all levels of the small intestine with the highest activity per milligram protein in the duodenum. The prostaglandins, when added directly to the assay, increased adenyl cyclase activity; the greatest effect (2-fold increase) was obtained with PGE(1) (maximal effect at 0.03 mM) and PGE(2). The prostaglandins also increased short-circuit current (SCC) in isolated guinea pig ileal mucosa, with PGE(1) and PGE(2) again giving the greatest effects. The prior addition of theophylline (10 mM) reduced the subsequent SCC response to PGE(1) and vice versa. It was concluded, therefore, that the SCC response to PGE(1), like the response to theophylline, represented active Cl secretion. CT increased adenyl cyclase activity in guinea pig and rabbit ileal mucosa when preincubated with the mucosa from 1 to 2.5 hr in vitro or for 2.5 hr in vivo but not when added directly to the assay. The increments in activity caused by PGE(1) and NaF were the same in CT-treated and control mucosa. Cyclic 3',5'-AMP concentration in rabbit ileal mucosa was increased 3.5-fold after a 2 hr preincubation with CT in vitro. Phosphodiesterase activity in the crude membrane fraction of the mucosa was unaffected by either CT or PGE(1). A variety of other agents including insulin, glucagon, parathormone, thyroid-stimulating hormone, L-thyroxine, thyrocalcitonin, vasopressin, and epinephrine all failed to change adenyl cyclase activity. It is concluded that CT and certain prostaglandins produce small intestinal fluid secretion by increasing mucosal adenyl cyclase activity, thereby stimulating an active secretory process.
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PMID:Stimulation of intestinal mucosal adenyl cyclase by cholera enterotoxin and prostaglandins. 432 9

The present studies were undertaken to determine the role, if any, of cyclic 3',5'-adenosine monophosphate (cyclic AMP) as a chemical inducer of rat liver alkaline phosphatase. Cholera enterotoxin, given intravenously to rats, led to a rapid rise in the activity of hepatic adenyl cyclase that was 7(1/2) times greater than control values in 6 h. Cyclic AMP levels were also significantly increased above control values while the activity of cyclic nucleotide phosphodiesterase was unchanged. Hepatic alkaline phosphatase activity was increased 5(1/2) times above control in 12 h, but its rise followed that of adenyl cyclase and cyclic AMP by several hours. Cycloheximide inhibited the rise of hepatic alkaline phosphatase but not that of adenyl cyclase. The administration of glucagon, a known stimulator of hepatic adenyl cyclase, and of dibutyryl cyclic AMP, led to similar striking increases in hepatic alkaline phosphatase activity. This alkaline phosphatase increase was blocked by the prior administration of cycloheximide. Bile duct ligation, a known stimulator of hepatic alkaline phosphatase activity, failed to produce any significant changes in adenyl cyclase or cyclic AMP. Concomitant treatment of rats with bile duct ligation and cholera enterotoxin or bile duct ligation and glucagon, had no additive effect on the increase in hepatic alkaline phosphatase activity, although the increase occurred earlier. These results suggest that: (a) cyclic AMP may act as an inducer of hepatic alkaline phosphatase: (b) the stimulation of hepatic alkaline phosphatase by cholera enterotoxin is mediated by cyclic AMP; (c) the rise in hepatic alkaline phosphatase following bile duct ligation is not mediated by cyclic AMP; (d) the same alkaline phosphatase in rat liver may be induced by two (or more) mechanisms, only one of which requires cyclic AMP.
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PMID:Alkaline phosphatase. Possible induction by cyclic AMP after cholera enterotoxin administration. 435 3


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