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)

The vicinity of several hormone-producing glands as part of the anatomy of the intestinal tract and the resulting interaction has been confirmed by the discovery of hormonal factors of a specifically gastro-intestinal origin. Today we are mainly interested in the interaction between intermediary metabolism and incretory intestinal function; this is characterized by the joint action of conventional glandular hormones such as insulin and pancreatic glucagon as well as by the incretion of diffuse intestinal organs, hormones such as secretin, pancreozymin, motilin, VIP and GIP. The latter are at present subject of active research with the object of discovering their physiological significance be it as tissue hormones or as humoral agents with a "long distance" impact; their role within pathophysiology is also of interest. GIP ("gastric inhibitory peptide"), apart form acting upon the intestinal tract, also causes a marked rise in insulin production; this GIP possibly is the factor responsible for the difference in glucose tolerance following i. v. or oral administration of glucose, something that scientists have been trying to discover for a long time. We have also endeavored to investigate somatostatin. This substance was originally discovered as a hypothalamic factor with inhibitory action on growth hormone secretion; in the meantime, however, cells containing and possibly also producing somatostatin have also been detected in the intestine and particularly in the islets of Langerhans (D-cells). Since somatostatin inhibits insulin secretion and especially glucagon release as well as the exretory functions of the stomach and of the pancreas, the significance of this hormone possibly is that of a tissue hormone with inhibitory action on adjacent cells. As factor inhibiting both endocrine and exocrine secretory processes it would combine these two complexes. The possible therapeutic significance of somatostatin administration to diabetics would lie in the saving of insulin. A third sector of present-day research deals with the interaction between the calcium metabolism and the hormones involved as well as the intestine. We know that patients suffering from primary hyperparathyroidism are prone to contract stomach ulcers and pancreatitis; patients with a gastrinoma and a hyperfunction of the epithelial bodies suffer from a Zollinger-Ellison-sindrome and this again suggests association with endocrine polyadenomatosis (Wermer syndrome). The inhibitory action of the parathormone antagonist calcitonin on the exocrine functions of the intestinal tract, such as the acid secretion of the stomach and the enzyme secretion of the pancreas, have already given rise to some considerations and experiments relative to treatment. It is to be hoped that because of all the joint observations cited above there will be better intergration of research both from the aspect of gastro-enterology and endocrinology. This might hopefully elucidate some of the unresolved problems ranging from basic research to practical application.
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PMID:[Interaction between gastrointestinal hormones and endocrine regulation]. 0 83

The inhibitory effect of glucagon on pancreatic exocrine secretion induced by endogenously released secretin was studied in 4 dogs with chronic pancreatic fistulas and open gastric fistulas. After a constant level of pancreatic secretion was established by intraduodenal hydrochloric acid perfusion (9 mEq/hr), glucagon (30 microng/kg-hr) was administered intravenously for 1 hr. Compared to a separate control study in which dogs received intraduodenal HC1 alone, glucagon caused a significant decrease in both pancreatic volume flow and bicarbonate output. Glucagon had no effect on pancreatic protein secretion, and circulating levels of endogenously released secretin remained unchanged. It is concluded that the inhibitory effect of glucagon on pancreatic secretion is not mediated through inhibition of secretin release. The chemical homology between glucagon and secretin suggests that glucagon may mediate its inhibitory action by competing with secretin at the level of the pancreatic receptor site.
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PMID:The effect of glucagon on pancreatic secretion and plasma secretin in dogs. 1 33

The clinical symptomatology of the Zollinger-Ellison syndrome and the pathologic anatomy of gastrinomas are reviewed. Experience with 17 patients with the Zollinger-Ellison syndrome is presented with special reference to stimulation tests (secretin, glucagon, calcium infusion, test meal) and to localization and immunohistologic, ultrastructural, and biochemical findings in gastrinomas. Multiple hormone production by the tumors is frequent. The ultrastructure and the Sephadex G-50 gel filtration patterns of immunoreactive gastrin in sera and tumors are not uniform and are not related to localization of the tumors in the pancreas or duodenum or to the gastrin concentration. Hyperplasia of the pancreatic islets is a frequent finding in gastrinoma patients, suggesting that hypergastrinemia may stimulate islet growth.
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PMID:Pathomorphologic, biochemical, and diagnostic aspects of gastrinomas (Zollinger-Ellison syndrome). 4 19

Porcine vasoactive intestinal peptide stimulated adenosine 3':5'-monophosphate (cyclic AMP) production in rat intestinal epithelial cells. The stimulation was dependent on time and temperature and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Under optimal conditions (at 15 degrees C, with 0.2 mM 3-isobutyl-1-methylaxanthine, at a cell concentration up to 18 microgram DNA/ml), the cyclic AMP production produced by vasoactive intestinal peptide was constant for 10 min and stopped after 15 min incubation, at either low (1 nM) or high (30 nM) concentration of the peptide. This plateau effect was demonstrated not to be due to an inactivation of vasoactive intestinal peptide in the medium nor to an alteration of receptors for the peptide. Cyclic AMP production was sensitive to a concentration as low as 0.1 nM vasoactive intestinal peptide. Maximal stimulation of cyclic AMP levels by vasoactive intestinal peptide was observed with 30 nM vasoactive intestinal peptide and represented an 11-fold increased above basal. The dorse-response curve was monophasic with a Km of 2.3 x 10(-9) M. No cooperative effects were detected by Hill analysis. The positive non-linear relationship observed between stimulation of cyclic AMP production and occupancy of binding site was not time-dependent as indicated by experiments performed after 15, 45 and 120 min incubation. Maximal and half-maximal responses were obtained at about 70% and 7% occupation of binding sites, respectively. Chicken vasoactive intestinal peptide and porcine secretin were agonists of porcine vasoactive intestinal peptide with a 6-times and a 120-times lower potency, respectively. Among secretin analogs that were found to have low affinity for vasoactive intestinal peptide binding sites, [4-alanine, 5-valine]secretin, that resembles vasoactive intestinal peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive peptide at the first seven amino acids at the N-terminal end, was a partial agonist of vasoactive intestinal peptide and others failed to stimulate cyclic AMP production. Glucagon (10microM), gastric inhibitory peptide (0.1 microM), substance, P, neurotensin, octapeptide of cholecystokinin, bovine pancreatic polypeptide, human gastrin I with leucine at residue 15, Leu-enkephalinand somatostatin (1 microM) did not alter cyclicAMP levels. Non-peptide mediators such as dopamine, serotonin, acetylcholine and histamine, tested at 10 microM, were also ineffective. Prostaglandins E2, E1 and isoproterenol, tested at 10 microM, induced an increase of cyclic AMP levels above basal but were 9.5, 13.7 and 17.5 times less efficient than vasoactive intestinal peptide, respectively. Thus vasoactive intestinal peptide is a unique stimulus of cyclic AMP production in rat intestinal epithelial cells.
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PMID:Interaction of vasoactive intestinal peptide with isolated intestinal epithelial cells from rat. 2. Characterization and structural requirements of the stimulatory effect of vasoactive intestinal peptide on production of adenosine 3':5'-monophosphate. 8 68

The lower oesophageal high pressure zone (HPZ) was studied in 5 non-refluxing and 3 refluxing Rhesus monkeys. The changes in HPZ and reflux status in response to infusion of various doses of secretin, cholecystokinin and glucagon were measured in all animals, and, in the 5 non-refluxing monkeys, after oesophagogastrectomy with replacement of the lower oesophagus by a stomach tube. All three hormones consistently produced a transient decrease in the HPZ pressure. The only change in response following oesophagagastrectomy and gastric tube replacement was a significant delay in the response to each hormone. Neither hormone infusion nor operation altered gastro-oesophageal reflux status. It appears that lower oesophageal competence in primates is more dependent on the presence of narrow, muscular, intra-abdominal tube than on a specialized segment of the lower oesophagus.
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PMID:Effect of gastrointestinal hormone infusions of lower oesophageal competence of rhesus monkeys. 9 6

The effects of vasoactive intestinal polypeptide (VIP), glucagon, and secretin on lower esophageal sphincter pressure were investigated in awake baboons. The three hormones were compared with respect to effect on (1) resting lower esophageal sphincter pressure and (2) maximal stimulatory response to pentagastrin. VIP was shown to reduce resting and pentagastrin-stimulated lower esophageal sphincter pressure with significantly greater potency than either secretin or glucagon. For reduction of resting lower esophageal sphincter pressure, the potency ratio of VIP to secretin was 16:1 and of VIP to glucagon was 32:1 (P less than 0.05). For inhibition of pentagastrin-stimulated sphincter pressure, the potency ratio of VIP to secretin was 32:1 and of VIP to glucagon was 64:1 (P less than 0.02). This demonstration of significantly increased potency of VIP over known inhibitory hormones strengthens the suggestion that VIP may have a physiologic role in the control of lower esophageal sphincter function.
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PMID:Effects of vasoactive intestinal polypeptide (VIP) on lower esophageal sphincter in awake baboons: comparison with glucagon and secretin. 11 May 70

Reliable and specific radioimmunoassays have been developed for the gut hormones secretin, gastrin, cholecystokinin, pancreatic glucagon, VIP, GIP, motilin, and enteroglucagon. Using these assays, the relative pattern of distribution of the gut hormones has been determined using the same bowel extracts for all measurements. VIP occurred in high concentration in all regions of the bowel, whereas secretin, GIP, motilin, and CCK were predominantly localised in the proximal small intestine. Pancreatic glucagon was almost exclusively confined to the pancreas. Like VIP, enteroglucagon also exhibited a wide pattern of distribution but was maximal in the ileum. The acid ethanol extraction method that was used was found to be unsuitable for gastrin. On gel chromatography of the extracts, motilin and VIP eluted as single molecular species in identical position to the pure porcine peptides. CCK, pancreatic glucagon, enteroglucagon and GIP were all multiform.
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PMID:Distribution of the gut hormones in the primate intestinal tract. 11 57

The effects of a number of peptides which are found in the gastrointestinal tract have been ascertained on the direct current recorded dorsal and ventral root responses of the isolated hemisected toad spinal cord. Motilin, substance P, bombesin, neurotensin, and thyrotropin releasing hormone had potent depolarizing actions on dorsal root terminals and motoneurons. These substances evoked discernable effects at concentrations as low as 10--7 M, or even lower with motilin. The effects of motilin, neurotensin, and thyrotropin-releasing hormone were greatly reduced or abolished by perfusion of the preparation with tetrodotoxin. Adrenocorticotrophic hormone, secretin, and pancreozymin (cholecystokinin) also depolarized dorsal root terminals and motoneurons. The effects of secretin and cholecystokinin were not abolished by tetrodotoxin. Leu- and Met-enkephalin had weak hyperpolarizing actions on the dorsal and ventral root potentials of repetitively stimulated preparations. Gastrin, gastric inhibitory peptide, glucagon, and somatostatin had no apparent effects on the responses of the preparation. Angiotensin and vasopressin both had rather weak depolarizing effects on the dorsal and ventral roots.
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PMID:Actions of various gastrointestinal peptides on the isolated amphibian spinal cord. 11 60

Angiography before and after the administration of Glucagon was performed in 33 adult patients with symptoms suggesting a pancreatic lesion. Preferently the pancreatographic effect was evaluated. The results were compared with those of the angiography following the administration of Secretin and Tolazoline. The pancreatographic effect was visualized in 70% of the patients examined with Glucagon and the rate of visualization of the effect with Secretin and Tolazoline was 60% and 74.5% respectively. The representation of the small vessels could be enhanced with Glugacon only in 15% for the arteries and in 12.5% for the veins, whereas using Secretin and Tolazoline the improvement raised up to 78% of the cases. -- The pancreatographic effect as an additional sign is useful in the differential diagnosis of the chronic pancreatitis (mottled) and the carcinoma of the pancreas (defect or absence of the effect).-- The superselective technique is recommendable. Using this method an improvement of the pancreatographic effect can be achieved already. In pharmacoangiography Tolazoline gives better results than Glucagon.
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PMID:[The pancreatographic effect during pharmacoangiography of the pancreas following the administration of glucagon (author's transl)]. 13 54

After a review on the historical development of morphological investigations of entero-endocrine cells, dating back to 1870, a detailed synoptical review of the current stage of findings in this field is given. At the present time nine different endocrine cell types can be distinguished in the epithelium of the gastrointestinal tract. Criteria for this differentiation are properties concerning specific staining methods, aldehyde-induced fluorescence, immunohistochemistry, and ultrastructure. From present results it is obvious that distinct cell types are responsible for the synthesis of defined polypeptide hormones (e.g. gastrin, secretin, enterogastrone). The metabolism of amines, in relation to the endocrine cells of the gastrointestinal tract is of particular interest here. Points investigated include the uniqueness of endocrine cells, with regard to the metabolism of biogenic amines ("APUD-cells") and the possibility of serotonin synthesis by a definite cell type, i.e. by the EC-cell ("enterochromaffin" cell). In our experimental animal, male Wistarrats, seven different entero-endocrine cell types can be discerned by ultrastructural means: EC-, ECL-, G-, AL-, EG-, D- and D1-cells. The I-cell (found in other species) can hardly be distinguished from the AL-cell by ultrastructural means and the S-cells, as found in other species, are not to be found at all. Only some of the cited cell types can be seen by fluorescence microscopy. After formaldehyde-treatment of the tissue, the "enterochromaffin" cell shows a yellow, serotonin-specific fluorescence. This cell corresponds in shape, number and distribution to the ultrastructurally defined EC-cell. EC-cells are found predominantly in the pyloric region and the duodenum and less frequently in the middle- and hindgut and the cardiac region; seldomly EC-cells are encountered in the oxyntic gland area of the stomach. In the rat gastro-intestinal tract, number and fluorescent intensity of EC-cells does not always correspond with the serotonin content of a certain region--sometimes the level of serotonin is largely determined by the mast cells, which in the rat also contain serotonin. For example, the high serotonin content of the oxyntic gland area, which contains very few EC-cells, has to be contributed nearly exclusively to mast cell serotonin. Mast cells can be domonstrated by fluorescence microscopy, due to their histamine content, after treatment of the tissue with o-phthalaldehyde (OPD). It seems likely that the histamine content, especially that of the so-called "atypical mast cells" of the mucosa, is inversely related to their respective serotonin content. --In addition to mast cells, OPD-treatment leads to a fluorescence in some of the entero-endocrine cells of the gastrointestinal epithelium. In the gastric epithelium these fluorescing cells should be regarded as histamine-containing ECL-cells and glucagon-containing AL-cells while in the colonic epithelium they are considered to be glucagon-containing AL-cells...
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PMID:[The endocrine cells of the gastrointestinal epithelium and the metabolism of biogenic amines in the gastrointestinal tract (author's transl)]. 13 9


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