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)

Extracts of homogenates of rat, mouse, rabbit, and human submaxillary salivary glands contain a significant quantity of a material with glucagon-like immunoreactivity. Fractionation of this material on columns of Sephadex G-100 reveals a single peak immediately following a gamma globulin marker but in advance of a rat growth hormone marker, crystalline amylase, and isotopically labeled porcine insulin and glucagon. This material, which is urea stable, shows identical immunoassay dilution curves when measured with the highly specific K-30 glucagon antiserum. Study of paired glands in vitro shows that low concentrations of glucose stimulate and high concentrations of glucose suppress release of this material. Arginine promotes brisk release in vitro. Somatostatin does not influence arginine-stimulated secretion and insignificantly suppresses basal release in vitro. These findings lend support to previous speculations that the salivary glands may possess endocrine as well as exocrine functions. Salivary gland glucagon may also be the source of circulating glucagon recently reported in pancreatectomized and eviscerated rats.
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PMID:Salivary gland hyperglycemic factor: an extrapancreatic source of glucagon-like material. 6 92

Recent data seem to support a tubular defect as the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon has been proposed by some to be an important factor in this phenomenon. To examine the role of glucagon as this "tubular dysfunction factor", we investigated the effect of intravenously infused glucagon on the fractional excretion of amylase and the tubular handling of a low molecular weight protein, beta2 microglobulin, in normal, healthy volunteers. At glucagon levels far in excess of those seen in pancreatitis, the clearance ratio of beta2 microglobulin relative to creatinine increased, whereas the clearance ratio of amylase relative to creatinine did not increase above the normal range. The dissociation between beta2 microglobulin clearance and amylase clearance allows one to question the theory that tubular dysfunction is the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon does not appear to be the sole factor responsible for the elevation of renal clearance of amylase relative to creatinine in acute pancreatitis.
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PMID:Effect of glucagon infusion on the renal clearance of amylase relative to creatinine. 8 90

A 53-year-old white woman developed diabetes mellitus, migratory erythema, and anemia, clinical features suggesting the presence of a "glucagonoma." Ten years earlier, after laparotomy and pancreatic biopsy, she had been told that she had an inoperable pancreatic carcinoma. Review of that biopsy together with current hormonal assay now confirms the diagnosis of glucagonoma. The recurrent peptic ulcer in this patient despite high levels of glucagon, a gastric inhibitory agent, is noted but not explained. An enhanced amylase-creatinine clearance ratio supports the notion that glucagon increases the clearances of amylase.
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PMID:Glucagonoma, chronic recurrent peptic ulcer disease, and enhanced amylase-creatinine clearance ratio. Report of a case with review of the literature. 9 10

Four-fold increases in cyclic AMP levels were observed 5 to 10 min after rat pancreatic fragments were incubated with 10-7 M secretin or 10-6 M vasoactive intestinal polypeptide (VIP), in addition to 10 mM theophylline. From dose-response curves it appears that, on a molar basis, the potency of secretin was 20 times higher than that of VIP. It is concluded that cyclic AMP is probably the intracellular messenger of both secretin and VIP in centroacinar cells. Pancreozymin, caerulein, and the C-terminal octapeptide of pancreozymin inhibited the production of cyclic AMP observed with secretin of VIP, suggesting that the first three peptides were acting at a binding site different from the agonists, but coupled with the same adenylate cyclase. In acinar cells, secretin was able to exert slight ecbolic effects, and was also able to potentiate the effect of maximal concentrations of pancreozymin, caerulein, or the C-terminal octapeptide of pancreozymin. There was no simple correlation between amylase output and cyclic AMP levels, and copious amylase secretion was elicited even at control levels of cyclic AMP. Glucagon was neither an agonist nor an antagonist of any of the other polypeptides tested.
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PMID:In vitro interactions of gastrointestinal hormones on cyclic adenosine 3':5'-monophosphate levels and amylase output in the rat pancreas. 16 79

We have prepared 125I-labeled physalaemin and have examined the kinetics, stoichiometry, and chemical specificity with which the labeled peptide binds to dispersed acini from guinea pig pancreas. Binding of 125I-labeled physalaemin was saturable, temperature-dependent, and reversible and reflected interaction of the labeled peptide with a single class of binding sites on the plasma membrane of pancreatic acinar cells. Each acinar cell possessed approximately 500 binding sites, and binding of the tracer to these sites could be inhibited by physalaemin [concentration for half-maximal effect (Kd), 2 nM], substance P (Kd, 5 nM), or eledoisin (Kd, 300 nM) but not by cholecystokinin, caerulein, bombesin, litorin, gastrin, secretin, vasoactive intestinal peptide, glucagon, somatostatin, neurotensin, bovine pancreatic polypeptide, leucine-enkephalin, methionine-enkephalin, atropine, or carbamylcholine. With physalaemin, substance P, and eledoisin, there was a close correlation between the relative potency for inhibition of binding of labeled physalaemin and that for stimulation of amylase secretion. For a given peptide, however, a 3-fold higher concentration was required for half-maximal inhibition of binding than for half-maximal stimulation of amylase secretion, calcium outflux, or cyclic GMP accumulation. These results indicate that dispersed acini from guinea pig pancreas possess a single class of receptors that interact with physalaemin, substance P, and eledoisin and that occupation of 45% of these receptors will cause a maximal biological response.
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PMID:Interaction of physalaemin, substance P, and eledoisin with specific membrane receptors on pancreatic acinar cells. 23 Apr 88

Several investigations in vivo and in vitro have shown that gastro-intestinal hormones stimulate insulin secretion. However, the reports on the insulinotropic activity of pancreozymin are contradictory. The conflicting results are probably due to the fact that pure native preparation of this hormone has not been obtained in "physiologic" doses. In the present study this problem has been investigated by exposing rat pancreas to caerulein in vitro. Caerulein, an active decapeptide isolated from the skin of the Australian amphibia Hyla caerulea, resembles pancreozymin in chemical structure, including C-terminus. This active polypeptide of nonmammalian origin has been shown to possess all the biological activities of pancreozymin. The present investigation was undertaken to evaluate the significance of the interactions of exocrine and endocrine pancreas using perfused rat pancreas in vitro. Biphasic insulin release was demonstrated with caerulein at concentrations higher than 1 ng/ml. Insulin response of the first phase was proportional to the dose up to 1 microgram/ml. The second phase of insulin release was, however, almost constant, regardless of the concentrations of caerulein. Release of glucagon was stimulated by the same concentrations of caerulein which stimulated insulin release. Maximal response of the pancreatic amylase and pancretic juice output were observed with 1 ng/ml of caerulein. With higher doses, significantly less secretory responses were observed. The dissociation of the response to caerulein between endocrine and exocrine pancreas was found.
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PMID:[Effect of caerulein on pancreatic endocrine and exocrine secretion from the perfused rat pancreas (author's transl)]. 34 78

The results of a double-blind trial of glucagon in 69 patients with acute pancreatitis are reported. In a subgroup of 59 patients statistical analysis showed no significant differences between the glucagon-treated (n = 29; 2 X 5 mg protamine-zinc glucagon intramuscularly per day) and the placebo-treated (n = 30) subjects for the following data: duration of pain left spontaneously and induced by palpation, amounts of analgesics and antispasmodics required by the patients, duration of hospital stay, amylase activities in serum and 24 hour urine collections. Mortality rates did not differ significantly between the glucagon-treated and the placebo-treated subjects in the total group of 69 patients and in the two subgroups of patients who were treated conservatively (n = 59) and those who underwent laparotomy because of severe peritonitis (n = 10). From the results of this study it is concluded that favourable effects of glucagon upon the course of acute pancreatitis--if they do exist--are not significant.
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PMID:Glucagon therapy in acute pancreatitis. Report of a double-blind trial. 34 59

Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these 'CPR-secretors' there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p less than 0.005) and amylase (r = 0.7, p less than 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.
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PMID:The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus. 34 40

The effects of highly purified natural porcine cholecystokinin (CCK) and synthetic caerulein on the rate of flow of pancreatic juice, the rate of output of amylase, and the rate of release of immunoreactive insulin (IRI) and immunoreactive glucagon (IRG) were simultaneously investigated in the isolated perfused rat pancreas. The maximal flow rate of pancreatic juice was obtained with concentrations of CCK ranging from 0.5 to 10 mU/ml, whereas amylase output was maximal at CCK concentrations from 1 to 10 mU/ml. Caerulein at concentrations of 0.05-1 ng/ml induced a similar maximal flow rate and amylase secretion. Supramaximal stimulatory concentrations of these peptides resulted in lower rates of release of fluid and amylase than with the maximally effective concentrations. Stimulation of IRI and IRG release was elicited only with concentrations of peptides supramaximal for effects on the exocrine responses. The demonstration of very similar discrepancies between the doses of caerulein required to elicit maximal exocrine responses and those required to elicit endocrine responses provide strong evidence that the pattern of the effect of the porcine CCK is accounted for by CCK itself. Although caerulein had no influence on IRI response when superimposed on 100 or 150 mg/100 ml glucose stimulation, preperfusion of caerulein led to a significant enhancement of IRI response to a subsequent glucose stimulation in both phases. The augmentation effect was completely separate from the direct IRI-stimulating effect of caerulein, because the CCK-like peptide requires no glucose for insulinotropic action. Because the concentrations of the peptides necessary for stimulation of endocrine responses were inhibitory in their effects on exocrine responses, it may be inferred that it is unlikely that the endocrine effect is physiologically important, though the results of caerulein for augmenting glucose-stimulated IRI release suggests a possible role for CCK in carbohydrate metabolism.
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PMID:Discrepancies between the doses of cholecystokinin or caerulein-stimulating exocrine and endocrine responses in perfused isolated rat pancreas. 37 41

The secretion of insulin, glucagon, pancreatic juice, and amylase in response to a 20-min iv infusion of synthetic caerulein were studied simultaneously in the anesthetized rat. Caerulein, a chemical analogue of cholecystokinin, was used in doses of 1-1000 ng/kg.min. The maximum stimulatory effect of caerulein on pancreatic juice volume and amylase output was obtained with doses of 10 ng/kg.min. With increasing doses, the effect decreased progressively. On the other hand, the release of insulin and glucagon was stimulated only by supramaximal doses of caerulein, which had little or no effect on pancreatic exocrine secretions. These results raised the question of whether, under physiological conditions, cholecystokinin regulates the secretory activity of the endocrine pancreas.
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PMID:Effect of caerulein on exocrine and endocrine pancreas in the rat. 38 84


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