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)

Tyrosine aminotransferase (TAT) induction by glucagon and dexamethasone in the liver of tumor-bearing chickens was studied and compared with induction in healthy animals. The transplantable tumor was caused by inoculation of cells from a cell line induced by MC29 avian leukosis virus. TAT was hardly detectable in tumor tissue of control and dexamethasone-treated chickens, but it was induced by glucagon to levels which were significant although very low when compared to those in host liver or the liver of non-tumor-bearing controls after glucagon treatment. Dexamethasone failed to induce TAT in host liver at 8 A.M. while it significantly indiced TAT in the normal liver at the same time of the day. Similar failure of TAT induction was not detectable when glucagon was used instead of dexamethasone. Furthermore, it was found that diurnal variations in basal and dexamethasone or glucagon-induced TAT levels are considerably mitigated in host liver as compared to those observed in the liver of healthy animals. The possible reasons for these findings are discussed.
Int J Cancer 1975 Dec 15
PMID:Tyrosine aminotransferase induction in normal and tumor-bearing chickens. 0 Mar 37

150-200 g heavy, Walker-carcinoma bearing, male Sprague-Dawley-rats showed rapid, tumour weight dependent, loss of liver glycogen until complete depletion in tumour groups heavier than 40 g/animal. Simultaneously the glycogen mobilization after massive glucagon stimulation, was successivly diminished and finally abolished in different groups with increasing tumor weight. Concomitantly the spontaneous and stimulated activity of liver phosphorylase a was found markedly reduced in advanced tumour cachexia, the extent of stimulation of liver phosphorylase a activity by intracardial injections of epinephrine not being altered. Tumour induced inhibition of glycogen mobilization thus appears to have been excluded. To account for the relative late pronounced hypoglycemia in peripherial rat blood in face of the early loss of liver glycogen, accelerated gluconeogenesis has been postulated. In accord with this spontaneous rise in liver tyrosine amino transferase was found in tumour bearing rats along with a doubled maximal stimulation value after medrol injection as compared to control groups. This behavior could not be shown for liver alanine aminotransferase and liver fructose 1,6-di-phosphatase. The former showed no differences between control and tumour groups neither of spontaneous nor of stimulated activity. The latter showed only a very reluctant rise after massive stimulation by triamcinolone for 3 days in the control groups, the tumour bearing groups showing no deviation from spontaneous control values.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976 Jan 02
PMID:[Biochemical investigations of cancer cachexia. II. Depletion of glycogenolysis and stimulation of gluconeogenesis in Walker carcinoma 256 bearing rats (author's transl)]. 0 45

Insulin, proinsulin, glucagon and gastrin were determined in extracts of tumors of 27 patients with pancreatic islet cell neoplasia of pancreas, in one patient with nesidioblastosis, in extracts of uninvolved portions of the pancreas in 11 of the tumor patients and of 15 control pancreases. Mean insulin concentration in solitary adenomas and in adenomas of patients with adenomatosis was higher than in control pancreases; however, in all but 1 patient the insulin concentration in neoplastic islet tissue was lower than in islet tissue of control pancreas, assuming islet volume is 1% of pancreas. The percentage of proinsulin was elevated in 52% of tumors. Adenoma insulin content correlated with increments of plasma insulin after tolbutamide administration. Insulin and proinsulin concentrations in pancreas uninvolved by tumor were not suppressed. Fasting plasma glucagon was elevated in patients with islet cell adenomatosis and in patients with islet cell carcinoma some of whom had multiple endocrine adenomatosis. The mean concentration of glucagon in tumors was lower than in control pancreases. Elevated concentration of gastrin was found in some adenomas. The data indicate: 1) insulin-secreting islet cell tumors have decreased storage capacity for insulin, 2) elevated concentration of proinsulin in tumors may be due to decreased capacity to store insulin and in some to decreased conversion of proinsulin to insulin as well, 3) tolbutamide stimulates the exaggerated release of a relatively constant fraction of insulin stored in adenomas. 4) solitary adenomas may contain excess amounts of pancreatic hormones in addition to insulin, 5) elevated plasma glucagon in patients with organic hyperinsulinism may indicate malignancy, microadenomatosis or multiple endocrine adenoma syndrome, and 6) chronic hyperinsulinism and hypoglycemia due to adenoma do not suppress insulin and proinsulin content of uninvolved pancreas.
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PMID:Insulin, proinsulin, glucagon and gastrin in pancreatic tumors and in plasma of patients with organic hyperinsulinism. 1 70

The examination of the regulation of the system of 3'-5' cyclic nucleotide monophosphates has only begun in cancer tissues. In human cancers, these studies are notably non-existent. However, in animal cancers, especially the Morris hepatomas, enough data has been gathered that, while risky, certain trends seem to begin to appear. Cyclic AMP is constant or lowered, while cyclic GMP is elevated in the fast growing hepatomas. Regulation of adenylate cyclase by protein hormones is reduced, while regulation by epinephrine may be increased. Binding of glucagon is decreased in the fast growing hepatomas. Guanylate cyclase, while being predominantly cytoplasmic in the normal liver, is predominantly membrane bound in the tumors. The liver enzyme is also readily stimulated by several chemical carcinogens. The cyclic GMP phosphodiesterases are decreased in these tumors; while the cAMP phosphodiesterases are increased. Although the cyclic nucleotide dependent protein kinases (histone as substrate) are altered in the hepatomas, observations of unique cyclic nucleotide binding proteins or cAMP independent protein kinases in cancer tissues may be of even greater significance for the development of or the maintenance of the neoplastic state of cells.
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PMID:Cyclic nucleotide metabolism in solid tumor tissues. 2 89

Adult rat parenchymal hepatocytes can be maintained in primary culture on floating collagen membranes of prolonged periods of time. In this system the enzyme tyrosine aminotransferase is induced by glucagon, (10(-6) to 10(-8) M) hydrocortisone (10(-5) to 10(-8) M), and cyclic adenosine 3':5'-monophosphate (cAMP) (10(-4) to 10(-5) M). Epinephrine (10(-4) M) induces the enzyme only in the presence of hydrocortisone. Addition of actinomycin D inhibited the induction of tyrosine aminotransferase by hydrocortisone and cAMP. Maintenance of the cultured hepatocytes in the presence of glucose (3g/liter) results in partial suppression of the inducing effects of glucagon and cAMP. Cyclic quanosine 3':5'-monophosphate does not mimic the effects of glucose. These results demonstrate that the phenomenon of glucose repression of enzyme induction, demonstrated in vivo in mammalian liver, is independent of changes in levels of serum hormones, which occur in vivo as a result of glucose administration. This study also demonstrates that glucose repression is not mediated by changes in intracellular levels of cAMP and cyclic quanosine 3':5'-monophosphate.
Cancer Res 1978 Jun
PMID:Hormonal regulation and the effects of glucose on tyrosine aminotransferase activity in adult rat hepatocytes cultured on floating collagen membranes. 2 9

The binding of labeled insulin to dissociated R3230AC mammary adenocarcinoma cells from diabetic and intact rats was investigated in vitro. At 20 degrees, specific binding (total binding minus binding in the presence of 1000-fold excess or 10(-6) M unlabeled insulin) reached a plateau at 45 to 60 min and was directly related to the number of cells used. Degradation of labeled insulin, as measured by trichloroacetic acid precipitation, was related to the number of cells used, was not prevented by trasylol or phenylmethylsulfonyl fluoride (general proteolytic enzyme inhibitors), but was prevented by addition of 1 to 2% bovine serum albumin to the incubation medium. Specificity of insulisulin, and desoctapeptide insulin were capable of competing for insulin binding in an order of potency related to their relative biological activity; prolactin and glucagon were unable to compete for insulin binding. Scatchard analysis of the binding data demonstrated a curvilinear-plot; specific binding (over the concentration range of 10(-11) to 10(-10) M insulin) showed a high affinity (Kd approximately 1 to 3 X 10(-10) M), and the estimated number of sites was greater in tumors from diabetic animals than in tumors from intact animals or intact animals given insulin prior to sacrifice. Reversibility of insulin binding was studied by dissociation experiments; dissociation was enhanced in the presence of added unlabeled insulin compared to dissociation examined under conditions of "infinite" dilutions only. Maximum dissociation of bound insulin was observed in the presence of 10(-7) M unlabeled insulin, with less of an effect at lower or higher concentrations of added insulin (no effect seen at 10(-10) M insulin). Two techniques were investigated for separating cells from unbound labeled insulin; the procedure using centrifugation was found to be more efficient. Thus, in the R3230AC mammary adenocarcinoma, data obtained on saturability, reversibility, and specificity of insulin binding indicate the existence of an insulin receptor with properties similar to those found in normal cells.
Cancer Res 1976 Nov
PMID:Identification and characterization of the insulin receptor in the R3230AC mammary adenocarcinoma of the rat. 13 40

Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations.
Cancer Res 1975 Mar
PMID:Comparative adenylate cyclase activities in homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h). 16 85

Rats (weight 150-200 g) bearing Walker-carcinoma showed tumour size dependent hypoglycemia, diminished mobilization of glycogen following glucagon stimulation and elevated values of the enzyme activity of glucose-6-(P)-ase. A further hormonal stimulation of this enzyme activity towards the values observed in normal rats after betamethasone stimulation was not possible. The values of the enzyme fructose-1,6-di-(P)-ase in liver of tumour bearing rats equalled those found in normal controls and did not show any rise after application of betamethasone. The serum levels of free fatty acids did not show any difference between normal controls and tumour bearing rats, and displayed an equal rise after intensive stimulation of peripheral lipolysis.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1976 Jan 02
PMID:[Biochemical investigations of cancer cachexia: I. Tumour induced changes of glycogenolysis and gluconeogenesis of Walker carcinoma bearing rats (author's transl)]. 17 91

Adenylate cyclase systems were examined in purified membrane preparations from normal rat liver and several Morris hepatomas with differing growth rates. All tumor membrane preparations had lower relative specific activities than did liver preparations. Liver adenylate cyclase was stimulated by fluoride, glucagon and guanyl-5'-yl imidodiphosphate [Gpp(NH)p]. Membranes from two slow-growing hepatomas (hepatomas 20 and 21) contained adenylate cyclase activities which are also stimulated by each of these three modulators. Membrane adenylate cyclases from several fast-growing hepatomas (hepatomas 3924A, 7777, 5123tc, and 9618A2) were marginally stimulated by glucagon but were readily stimulated by fluoride and Gpp(NH)p. Examination of the highly specific binding of 125I-glucagon to the various membrane preparations revealed much less binding in all the tumor membranes than in liver membranes. More detailed kinetic examination of membranes prepared from liver, slow-growing hepatoma 21 (which had reasonable binding to and stimulation by glucagon), and fast-growing hepatoma 3924A (which had marginal binding to and stimulation by glucagon) revealed major differences in rates of cyclic adenosine 3':5'-monophosphate production in the absence and presence of glucagon, Gpp(NH)p, and glucagon plus Gpp(NH)p and in the combined alteration of magnesium:adenosine 5'-triphosphate ratio and temperatures. The different kinetic characteristics in the hepatoma adenylate cyclase systems may be due to different structural characteristics of the tumor membranes or may be due to altered hormonal receptors, catalytic units, or receptor-catalytic unit interrelationships within the tumor membrane.
Cancer Res 1976 May
PMID:Regulation of the adenylate cyclase system in transplantable hepatomas. 17 31

The glucagonoma syndrome is a rare clinical condition characterized by a distinctive cutaneous eruption associated with a glucagon-secreting islet cell neoplasm of the pancreas. A 19-year-old woman manifested typical features of this condition: a polymorphous skin eruption with characteristic distribution of lesions in perioral and paragenital regions; lesions in sites of cutaneous trauma; a skin biopsy that showed epidermal cleavage; glossitis; weight loss; mild anemia; abnormal glucose tolerance test results. Plasma glucagon levels, determined by radioimmunoassay, were approximately five times normal. Angiography indicated a pancreatic tumor with liver metastases. Islet cell origin was confirmed histologically. It is hoped that wider recognition of the distinctive clinical features of this syndrome will result in earlier detection and possible surgical cure of the underlying malignancy.
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PMID:The glucagonoma syndrome. A distinctive cutaneous marker of systemic disease. 20 56


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