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 glucagon-producing pancreatic tumors or glucagonomas are among the rarest forms of islet cell tumors; most are malignant and usually produce a definite clinical syndrome. Mild diabetes mellitus, weight loss, and anemia usually accompany the syndrome. However, only the presence of a peculiar cutaneous rash (necrolytic migratory erythema) and the finding of hyperglucagonemia on assay are reliable diagnostic features of the syndrome. Selective, celiac axis arteriography is the most valuable preoperative technique for localizing these neoplasms and their common liver metastases. Immunohistochemical and ultrastructural examinations are particularly helpful in defining the tumor cell nature (alpha-2 islet cell) and the peptide content (glucagon). When the tumor is benign (less than 30%), complete operative removal results in lasting cure; for malignant forms, surgical therapy is mainly palliative, and adjunctive chemotherapy should be administered. In this report, the importance of clinical recognition and operative and chemotherapeutic responses is illustrated in two patients. In each case, the characteristic dermatitis, diabetes mellitus, weight loss, anemia, and elevated plasmatic glucagon were present. Both patients had their tumors localized by selective angiography and underwent operative removal of the primary pancreatic lesion. In the case of benign glucagonoma, surgical excision was curative. In the malignant one, cytoreductive surgery plus adjunctive chemotherapy (dimethyltriazenomidazole-carboxamide resulted in prolonged survival and significant clinical improvement. Follow-up with serum glucagon assay has been useful in monitoring recurrence.
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PMID:Response of glucagonomas to surgical excision and chemotherapy. Report of two cases and review of the literature. 254 27

In segmental-pancreas transplantation the body and tail of the pancreas are used. In an experimental study in dogs, the effects of sequentially conducted removal of the right pancreatic lobe (pancreatic head), duct obliteration, celiac denervation, and autotransplantation were studied according to a crossover design. Two groups of dogs were studied. In both groups the right lobe of the pancreas was removed at primary operation, and the duct of the transected left lobe (body and tail) was injected with fibrin sealant. The left lobe was completely freed from surrounding tissue (celiac denervation) in group 1 (n = 9), and the innervation of the left lobe was left intact in group 2 (n = 8). At 12 wk, two dogs in group 1 and four dogs in group 2 underwent successful autotransplantation of the left lobe. Pancreatic hormone secretion was stimulated by intravenous glucose injection and test-meal administration before primary operation and at 11 and 18 wk thereafter. The combination of removal of the right lobe and duct obliteration led to a decrease in glucose tolerance at both stimulation tests and a decrease in peripheral insulin release after intravenous glucose injection. At test-meal administration, no change in insulin and glucagon levels was demonstrated. If celiac denervation was added, similar results were obtained based on the understanding that the peripheral insulin release after the test meal was significantly elevated. Meal-stimulated pancreatic polypeptide response was abolished in both groups. Removal of the right lobe leads to parasympathic denervation of the left lobe, and celiac denervation mainly interferes with alpha-adrenergic innervation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Crossover study on effects of duct obliteration, celiac denervation, and autotransplantation on glucose- and meal-stimulated insulin, glucagon, and pancreatic polypeptide levels. 264 31

Duplex ultrasound scanning has been used to assess mesenteric blood flow in normal and disease states. To investigate this technique we studied nine normal volunteers at rest and under conditions known to modify intestinal blood flow. After a baseline mesenteric duplex scan, each subject was given one of three treatments in random order: (1) test meal (710 kcal), (2) intravenous glucagon (40 micrograms/min), or (3) intravenous vasopressin (0.2 units/min). Peak systolic and diastolic velocities and vessel diameters were measured at intervals after treatment in the celiac and the superior mesenteric arteries (SMAs) and the right common carotid artery. Resting velocities did not differ among the groups. Peak systolic velocity increased significantly in both celiac and SMAs after the meal, with maximal changes in the celiac artery preceding those in the SMA in most subjects. Early diastolic flow reversal in the SMA was consistently lost after the meal (eight of nine subjects). Velocity changes after glucagon closely paralleled those after the meal. Vasopressin produced significant decreases in peak systolic velocity in both visceral vessels. No changes in vessel diameter were noted after any treatment. Coefficient of variation for repeated measures of peak velocities was 19% in the celiac and 12% to 16% in the SMA and the common carotid. The coefficient of variation for repeated measurements of arterial diameter was 6% to 8% in the SMA and 11% in the celiac artery. Clinically relevant changes in mesenteric hemodynamics can be reproducibly detected and quantitated by means of current duplex ultrasound technology. The similarities between the visceral arterial responses to a meal and glucagon are of interest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Duplex ultrasound measurement of changes in mesenteric flow velocity with pharmacologic and physiologic alteration of intestinal blood flow in man. 264 79

Necrolytic migratory erythema is the distinctive skin rash of the glucagonoma syndrome. Its presence is virtually pathognomonic of a glucagon-producing pancreatic islet cell neoplasm. Results of a study of a patient with hyperglucagonemia and necrolytic migratory erythema complicating untreated celiac disease are reported. Whereas pancreatic glucagon was only mildly elevated, there was marked elevation of enteroglucagon. Immunofluorescence staining demonstrated numerous (19.6 cells per square millimeter of mucosa) enteroglucagon-positive small intestinal crypt cells. Treatment with gluten-free diet not only resulted in resolution of malabsorption and improvement in small intestinal histology but was paralleled by disappearance of necrolytic migratory erythema, normalization of plasma glucagon levels, and marked reduction in the number of enteroglucagon-producing crypt cells (0.2/mm2 mucosa). The findings demonstrate that necrolytic migratory erythema is not an exclusively paraneoplastic phenomenon and that it can occur in association with excess production of enteroglucagon by the intestinal mucosa.
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PMID:Necrolytic migratory erythema with elevated plasma enteroglucagon in celiac disease. 270 19

A 46-year-old man had a 7-year history of severe rash, which was then diagnosed as necrolytic migratory erythema. He had a weight loss of 6 kg, abnormal glucose tolerance test findings, anemia, glossitis, hair loss, and hypoproteinemia. Plasma amino acids levels were significantly decreased, and the fasting plasma glucagon (IRG) level was high at 5000 to 8000 pg/ml. Circulating IRG significantly increased after oral glucose loading, meal ingestion, and arginine infusion, and decreased with somatostatin infusion and insulin-induced hypoglycemia. No other gut or pancreatic hormone levels in plasma were elevated. Plasma IRG was eluted by gel-filtration, mainly in the position of true glucagon (MW 3500) by antiserum 30K. The rash was markedly improved after infusion of amino acids. Computerized tomography (CT) scan and celiac angiography revealed a large pancreatic tumor with multiple liver and lymph node metastases. The pancreatic tumor was totally resected, and was identified as glucagonoma by immunohistochemical technique. Since the plasma IRG levels remained high after surgery, the patient received dimethyltriazenoimidazole carboxamide therapy. After several courses of this treatment, plasma IRG levels decreased to 1000 to 2000 pg/ml, and the hepatic metastases were remarkably diminished in size.
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PMID:A functional study of a case of glucagonoma exhibiting typical glucagonoma syndrome. 286 23

Directional blood flow in pancreatic islets may be important for regulation of islet hormone release. We therefore perfused an isolated canine pancreas via the celiac artery (arterial perfusion) and then via the portal vein (venous perfusion) in the same pancreas. Basal insulin and glucagon levels and their rate of release in response to 10 mM arginine, 11 mM glucose, 500 pg/ml somatostatin, or 500 pg/ml glucagon were similar under both conditions. However, the inhibition of glucagon release due to somatostatin and its recovery after the cessation of somatostatin infusion was poor in the case of venous perfusion. The basal somatostatin level and its release in response to 10 mM arginine, 11 mM glucose, and 500 pg/ml glucagon during venous perfusion was significantly higher than that during arterial perfusion. From these results, it is speculated that the directional blood flow in pancreatic islets may not be essential for regulation of hormone release from the canine pancreas or that such directionality does not exist in canine pancreatic islets, and that a considerable portion of released somatostatin may be taken up by the pancreas located downstream--probably in the exocrine pancreas.
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PMID:Hormone release from pancreatic islets perfused from venous side. 287 56

Continuous measurement of portal vein and hepatic artery blood flows during physiological experimental conditions, even in large animals, poses difficult problems. We report the successful use of miniaturized flow probes and pulsed Doppler flowmetry for chronic monitoring of hepatic artery and portal vein flows in intact unrestrained rats and describe the probe construction and implantation. Proportionality between portal vein velocity and portal flow was made possible by a technique for stabilizing the diameter of the venous segment from which velocity is recorded. The accuracy of the method in detecting changes in portal vein flow was established by the high statistically significant correlation between changes in velocity recorded simultaneously from portal vein and superior mesenteric artery in a series of rats with ligated celiac and inferior mesenteric arteries. In these preparations all portal vein flow is derived from the superior mesenteric artery. Complex dynamic changes in the hepatic circulation of conscious unrestrained rats were recorded in response to systemic injections of glucagon and angiotensin II. In the resting state several characteristic velocity patterns were recorded from the portal vein. Oscillations linked to respiration were not observed while the animals rested quietly but were noted during sleep and anesthesia. Two hitherto unrecognized patterns produced respectively by the pulsations of the superior mesenteric artery and by spontaneous contractions of the portal vein were also observed. The method described here provides the first opportunity to study hepatic circulation in chronically instrumented rats during physiological experimental conditions.
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PMID:Continuous monitoring of portal vein and hepatic artery hemodynamics in unrestrained rats. 297 Feb 28

The isolated perfused human pancreas was employed as a model in which electrical stimulation of the celiac mixed neural bundle was performed in the presence or absence of selective neural blockers. The insulin and glucagon responses to hyperglycemia alone or in the presence of splanchnic nerve stimulation were similar in magnitude to the results obtained in a preliminary report on isolated human pancreatic function and in studies using animal models. Stimulation of the celiac neural bundle in the presence of hyperglycemia resulted in an inhibition of insulin release and in an augmentation of glucagon release. alpha-adrenergic stimulation resulted in a strong suppression of insulin secretion and a mild suppression of glucagon secretion. beta-adrenergic fiber stimulation caused a mild augmentation of both insulin and glucagon release, whereas the cholinergic fibers strongly stimulated both alpha- and beta-cell secretion. The predominant effects of celiac neural bundle stimulation are insulin inhibition by was of an alpha-adrenergic effect and glucagon stimulation by way of a cholinergic effect. Thus, in this in vitro human model, our data confirm that the splanchnic innervation of the pancreas has a potent regulatory role on pancreatic hormone release in human subjects.
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PMID:Splanchnic neural regulation of insulin and glucagon secretion in the isolated perfused human pancreas. 354 57

Regulation of pancreatic exocrine secretion is comprised of a complex interplay between hormonal and nervous mechanisms. Stimulatory gut hormones which act via the circulation include secretin, CCK, gastrin and bombesin, while VIP operates through peptidergic nervous release. Pancreatic polypeptide and glucagon are two examples of circulating inhibitory hormones while inhibition by somatostatin is through a paracrine release mechanism. Although the effects of vagal cholinergic nerves have been previously thought to be indirect through hormone release evidence is now accumulating for a direct role. Altered hormone release has been noted in chronic pancreatic insufficiency, cystic fibrosis and coeliac disease and may contribute in an important way to the pathophysiology of these malabsorptive disorders.
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PMID:Neuro-hormonal control of pancreatic function in man and its failure. 613 50

Secretory protein-I (SP-I) of parathyroid glands and chromogranin A ( CGA ) of adrenal medullary chromaffin cells are chemically similar if not identical proteins. Both proteins are contained within secretory granules and appear to be cosecreted with granule contents, for example, in the parathyroid with PTH and in the adrenal with epinephrine and dopamine beta-hydroxylase. Antisera to bovine SP-I and porcine CGA , together with antisera to a variety of peptide hormones, were used in an immunofluorescence study of rat tissues in order to determine the probable distribution and cellular localization of these proteins. In addition to their previously demonstrated presence in parathyroid and adrenal cells, the SP-I/ CGA protein family was detected in cells of the thyroid that contained calcitonin and often SRIF but not thyroglobulin; in cells of the anterior pituitary staining for the alpha-subunit of TSH/FSH/LH but not in cells staining for GH, PRL, ACTH, or beta-endorphin; in pancreatic islet cells staining for SRIF and pancreatic polypeptide-related peptides, but not for insulin or glucagon; in the celiac and mesenteric ganglia in cells some of which contained SRIF; and in the gastric antrum in cells containing SRIF, but not gastrin. SP-I/ CGA was not detected in cells of the liver, kidney, parotid gland, or acinar pancreas or in the intermediate or posterior lobes of the pituitary. These results suggest that this protein family enjoys a widespread but highly restricted distribution in many different endocrine-peptide cells of the rat, many that are believed to be of the APUD cell series. The possibility is raised that SP-I/ CGA plays some physiological role in the secretory process or exerts an effect of its own in the periphery after secretion.
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PMID:Selective localization of the parathyroid secretory protein-I/adrenal medulla chromogranin A protein family in a wide variety of endocrine cells of the rat. 623 31


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