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)

Isolation of thymocytes from rat thymus resulted in the disappearance of the high activity of ornithine decarboxylase (ODC) that characterizes the thymus of young rats, together with the appearance of an antizyme-like ODC inhibiting activity, which showed a chromatographic profile that resembled that of dexamethasone-treated rat thymus. Omission of serum or addition of dexamethasone or spermidine did not affect appreciably the extent of the antizyme-like activity. On the other hand, a variety of hormonal effectors, i.e. insulin, glucagon, adrenalin and T3, as well as the phorbol ester, PMA or the mitogen, concanavalin A (Con A) induced ODC activity in cultured thymocytes together with the disappearance of the antizyme-like activity. A paradoxical, transient induction of ODC was caused by the transcriptional inhibitor, actinomycin D. Complexed ODC was detected in rat thymus, but not in thymocytes, either quiescent or stimulated by mitogens. These results indicate that thymic lymphocytes can express either ODC activity or its inhibitor depending on the hormonal and proliferative status of the cells.
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PMID:Ornithine decarboxylase and ornithine decarboxylase-inhibiting activity in rat thymocytes. 147 63

The maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.
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PMID:Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat. 256 32

Adenylate cyclase of homogenates or lysates of mouse and rat lymphoid tissues was activated by the addition of fluoride ion, epinephrine, or norepinephrine, but not by any of several other hormones. The catecholamine stimulation was characterized as beta-adrenergic. This activity was localized in the small lymphoid cells, was greater in thymic than in splenic or mesenteric node cells, and also was greater in mouse than in rat cells. Catecholamine-stimulated activity of mouse thymocytes remained constant from the 17-19th day of fetal development to 5 weeks after birth; it subsequently decreased to about one-half of the activity by 7-8 weeks. Similar decreases with age occurred in mouse spleen and rat thymus. In contrast, the glucagon-stimulated activity of rat liver increased during a similar period. Hypophysectomy of rats at 3 weeks did not influence the amount of cyclase activity of thymocytes assayed at 7 weeks. When intact mouse thymocytes were first incubated in a culture medium at 37 degrees C with epinephrine or norepinephrine, a second addition of catecholamine after cell lysis no longer stimulated the enzymes. This loss of stimulation was selective, since basal activity and stimulation by fluoride ion were not affected. Incubation of intact cells with phytohemagglutinin markedly decreased the activity of lysates, whether assayed in the presence or absence of catecholamine or fluoride. In contrast, phytohemagglutinin added directly to the assay had no effect. No alternations occurred in adenylate cyclase activity as a result of the incubation of a 1:1 mixture of thymocytes from two strains of mice selected for the capacity of the cells to produce a mixed lymphocyte response.
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PMID:Properties of adenylate cyclase of lymphoid cells. 528 May 25

A series of 25 apudomas of the gastrointestinal tract (22 cases), bronchus (2 cases), and thymus (1 case) were subjected to staining with silver impregnation (Masson-Fontana and Grimelius) techniques and with the commercial immunoperoxidase kits for the peptide hormones adrenocorticotropin, calcitonin, gastrin, glucagon, growth hormone, human chorionic gonadotropin (hCG), insulin, somatostatin, and vasoactive intestinal peptide. Of the tumors studied, 16 were regarded as malignant, and 5 of the patients showed clinical symptoms due to inappropriate hormone secretion. A total of 16 tumors contained cells positive for 1 or more (6 were multihormonal) of the hormones studied. One bronchial carcinoid stained for hCG, which has not been previously reported. In addition, one of the rectal carcinoids contained somatostatin-positive cells, only once described previously. The thymic tumor proved frankly malignant, most probably identical to the oat-cell carcinoma recently described. The findings also substantiate the recent suggestion that gastrointestinal carcinoids cannot be adequately classified on the basis of silver stains only and strongly advocate the use of the immunoperoxidase kits in routine assessments of all the endocrinologically active tumors, whatever their localization might be.
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PMID:Stainability of the peptide hormones in gastrointestinal apudomas as demonstrated by immunoperoxidase kits. 614 78

To show that glucagon, glucagonlike immunoreactivity (GLI), and insulin are synthetized by organs other than the pancreas and the gastrointestinal tract, different rat tissue acid-ethanol extracts were obtained and analyzed by immunoassay using specific antisera. Significant amounts of glucagon were found in the gastrointestinal tract (44.77 +/- 5.4 ng), salivary glands (1.50 +/- 0.17 ng), thymus (2.80 +/- 0.46 ng), thyroid (0.25 +/- 0.02 ng), and adrenal glands (0.25 +/- 0.06 ng). Whereas GLI appeared in the gut mucosa, adrenal and salivary glands, genuine insulin was detected only in the pancreas. Aliquots of the tissue extracts, fractionated on Bio Gel P 30 columns, gave a 3,500 mol wt immunoreactive (30 K) peak that behaved as pancreatic glucagon on acrylamide gel electrophoresis and displaced 125I-labeled glucagon previously bound to its hepatic receptors. Arginine, epinephrine, and low glucose concentrations stimulated glucagon release from parotid, thymus, and thyroid. Active glucagon biosynthesis by these organs was established by the incorporation of L-[3H]tryptophan into a 3,500 mol wt polypeptide with specific immune reaction with 30 K antiserum. These results suggest that different rat tissues can contribute to the circulating levels of glucagon and GLI and therefore to metabolic homeostasis.
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PMID:Tissue distribution of glucagon, glucagonlike immunoreactivity, and insulin in the rat. 698 65

During their development in the thymus, T cells acquire interleukin (IL)-2 and IL-4 inducibility in a developmentally controlled manner. Although the role of IL-2 and IL-4 in T cell development is still unclear, several reports indicated that IL-2/IL-2R and IL-4/IL-4R interactions in the thymus could play an important role in T cell development. The presence of vasoactive intestinal peptide (VIP)-immunoreactive cells and nerve fibers in the thymus suggests the possible local release of the neuropeptide in the thymic microenvironment. VIP has been previously reported to inhibit IL-2 and IL-4 production, as well as the proliferation of mitogen- or antigen-stimulated peripheral T cells. Here we report on the effect of VIP on IL-2 and IL-4 production by and proliferation of murine thymocytes stimulated through the TCR/CD3 receptor. VIP inhibited both IL-2 and IL-4 production, as well as the proliferation of murine thymocytes in a dose-dependent and specific manner. Structurally related peptides such as secretin or glucagon had little or no inhibitory activity. The intact VIP molecule was required for the inhibitory effect, since amino- or carboxy-terminal fragments did not inhibit IL-2 production. The inhibitory effect of VIP was observed for VIP additions up to 12 h after the initiation of the cultures, and incubations longer than 3 h were required for maximum inhibitory effects. Through its downregulatory effect on IL-2 and IL-4 production, locally released VIP could potentially affect T cell development within the thymus.
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PMID:Vasoactive intestinal peptide inhibits interleukin (IL)-2 and IL-4 production in murine thymocytes activated via the TCR/CD3 complex. 792 4

In addition to glucagon's role in regulating glucose production from the liver, a number of extrahepatic effects of glucagon have been reported. We have therefore examined various rat tissues for glucagon receptor mRNA expression. In liver, kidney, heart, adipose tissue, spleen, pancreatic islets, ovary, and thymus, glucagon receptor mRNA expression was found to be relatively abundant whereas lower levels were detected in stomach, small intestine, adrenal gland, thyroid, and skeletal muscle. The presence of glucagon receptor mRNA in tissues known to be responsive to glucagon suggests that these effects are mediated by specific glucagon receptors. Furthermore, the finding of glucagon receptor mRNA in the spleen, thymus, thyroid, adrenal gland, ovary, and skeletal muscle, where glucagon is not generally considered to act, indicates that there may be novel actions of glucagon that have yet to be determined.
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PMID:Glucagon receptor mRNA distribution in rat tissues. 853 3

The objective of the present studies was to determine whether the existence of functional glucagon receptors could be established on lympoid cells. The glucagon receptor, which positively regulates adenylate cyclase, is a member of the superfamily of seven transmembrane domain G-protein coupled receptors. Previously reported specific binding with [125I]-glucagon to a variety of lymphoid and myeloid cell preparations suggests that glucagon receptors are expressed within the immune system. In the present study, Northern analysis of polyA RNA isolated from primary mouse and rat derived lymphoid tissues and lymphoid cell lines EL-4.IL-2, Jurkat E6-1, CH12LX, and BCL1-3B3 cells were probed with a 32P-labeled human hepatic glucagon receptor. Mouse spleen and thymus, rat spleen, and the B cell line, CH12LX, all possessed a single 1.5 kb fragment (BCL1-3B3, 1.4 kb) which hybridized to the glucagon receptor cDNA probe, as compared to mouse liver which exhibited a 2.8 kb fragment. EL-4.IL-2 and Jurkat E6-1 cells possessed a 3.7 kb fragment with an additional 2.75 kb band present in Jurkat E6-1 cells. Treatment of mouse splenocytes and T- and B-lymphoma cells with glucagon (0 - 100 nM) produced a dose-dependent enhancement in intracellular cAMP which was maximal at 5 min post treatment followed by a gradual decline. Direct addition of glucagon to spleen cell cultures over a broad concentration range produced no effect on either lymphoproliferation following stimulation with anti-CD3 mAb, or LPS nor on the antibody forming cell (AFC) response to sRBC. Conversely, glucagon effectively reversed the suppression of the sRBC AFC response produced by delta9-tetrahydocannabinol (delta9-THC), and partially reversed the suppression produced by 2',3'-dideoxyadenosine, both of which are potent inhibitors of adenylate cyclase. These studies confirm the expression of functional glucagon receptors on lymphoid cells.
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PMID:Expression of functional glucagon receptors on lymphoid cells. 863 21

Following acute central nervous system myelin injury, immunoreactive myelin basic protein (MBP) has been detected in the cerebrospinal fluid, blood and urine. In order to clarify the fate of MBP in the circulation, distribution and degradation of intravenously injected bovine MBP was followed in anaestethized rats for 5 to 240 min by using 125I-labelled MBP. Five minutes after injection of a dose of 60-400 ng of MBP, 44% of the label was recovered in the liver, 6.3% in the kidneys, 4.7% in the lungs and 15% in the blood circulation, the corresponding figures at a dose of 0.8 mg being 51, 7.4, 0.8 and 22%. The liver discarded the label fastest, 3% of the dose remaining 4 h after injection. The amount of label in urine increased simultaneously, the recovery at 4 h being 5.5% of the lower and 4.2% of the higher MBP dose. The percentage of total dose of the label per gram of tissue at 5 min (= distribution percentage, DP-5) was 3-4% in the liver and kidney and 1.6% in the spleen. The label content in the pancreas was increased at 15-60 min, compared to the DP-5 of 0.3% with a two-fold maximum at 30 min. The duodenum concentrated MBP in a similar manner as the pancreas but not as extensively. The DP-5 of 0.1% in the thymus was concentrated two-fold with a maximum at 60 min. A slight concentration occurred in the heart. The DP-5 of 0.03% in muscle, testis and brain was concentrated 3-fold at 60 min, 3.6-fold at 60-240 min and 2-fold at 30-60 min in the aforementioned tissues, respectively. In spite of degradation of the label in tissues, the distribution of high molecular weight (HMW = TCA-precipitable) MBP was similar. Other experiments showed that the kidney, lung and duodenum contained most of the HMW MBP at 20 h. Upon continuous release of MBP, the pancrease, thymus, duodenum, muscle and testis would thus cumulatively concentrate MBP, and the kidney, lung and duodenum would be quantitatively most affected. MBP was previously shown to enter into cells of pancreative islets and to stimulate insulin and glucagon release. It could have biological effects in other tissues as well. These effects could explain some peripheral symptoms present in neurological disorders.
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PMID:Disappearance of 125I-labelled myelin basic protein from blood circulation and its degradation and accumulation in various tissues in rats. 888 Jun 87

The regulation of glucose metabolism by glucagon and GLP-1 is well established, but novel functions for these and other proglucagon-derived peptides are less well defined. This paper highlights the diversity of both GLP-1 and glucagon activity by studying the tissue distribution of glucagon and GLP-1 receptor gene expression by both Southern blot analysis of RT-PCR products and nuclease protection assays. By Southern blot analysis of RT-PCR products, GLP-1 receptor mRNA was detected in lung, hypothalamus, hippocampus, cerebral cortex, kidney, pancreas, and throughout the gastrointestinal tract. Glucagon receptor expression was detected in liver, kidney, spleen, thymus, adrenal glands, pancreas, cerebral cortex, lung, and throughout the gastrointestinal tract. Nuclease protection assay revealed glucagon receptor expression to be highest in liver and kidney, whereas GLP-1 receptor expression was only detected by protection assay in lung, stomach, and large bowel. Despite previous evidence that other receptors for proglucagon-derived peptides may exist, no evidence of novel receptors or multiple isoforms of the glucagon and GLP-1 receptors was found, indicating that the two cloned receptors may mediate all the effects of proglucagon-derived peptides, or that novel receptors may share less homology with the glucagon and GLP-1 receptors than previously anticipated.
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PMID:Tissue distribution of rat glucagon receptor and GLP-1 receptor gene expression. 972 98


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