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 multisystem involvement in acute pancreatitis (AP) is a reflection of the pancreatic gland's capacity to produce a number of potent vasoactive peptides, hormones, and enzymes. The various prognostic criteria are early evaluations of these metabolic derangements. The pathogenesis of hypocalcemia, long recognized as an indicator of severity of AP, is multifactorial. Imbalances of parathyroid hormone (PTH)-calcitonin, the interactions of glucagon, gastrin and other pancreatic hormones with PTH-calcitonin, the role of free fatty acids in binding serum calcium with albumin, and the translocation of calcium ion in muscles and liver, have been recently described but remain conflicting theories. Yet, the time-honored theory of calcium-soap formation enjoys wide acceptance. Hyperglycemia, hypoglycemia, and occasional ketoacidosis in acute pancreatitis have been studied thoroughly. The complex cause-and-effect relationship between hyperlipidemia with acute pancreatitis needs further study. The coagulation abnormalities seem to be initiated by activated trypsin, and their role in microvascular coagulation appears to form a unifying hypothesis for major organ dysfunction, but this requires further investigation. Adult respiratory distress syndrome may be the result of active enzymes that digest pulmonary surfactant and/or microvascular thrombosis. The depression of cardiac function and shock are suspected to be secondary to vasoactive peptides such as bradykinin, or myocardial depressant factor, whose structure has yet to be elucidated. The renin-angiotensin alterations and renal complications in acute pancreatitis have received scant attention in the literature. The onset of moderate visual disturbances, or even blindness, in a patient with acute pancreatitis as a result of retinal vessel thrombosis is fortunately uncommon. Rare but interesting are the manifestations such as subcutaneous fat necrosis, arthralgia, and pancreatic encephalopathy. Despite the extensive literature on the complexities of the pathogenesis of complications of acute pancreatitis, there have been very few advances in the prevention and management of specific complications. It is hoped that further work on modification of enzymatic disturbances induced in acute pancreatitis will result in its effective treatment and prevention of serious complications.
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PMID:Systemic complications of acute pancreatitis. 328

Factors capable of stimulating DNA synthesis in rat hepatocytes (stimulating activity) were detected in the portal serum of patients after liver resection. The stimulatory factors were fractionated by gel filtration into four fractions with the molecular weights of 45,000-60,000 (fraction A), 1,500-2,500 (fraction B), 800-900 (fraction C), and about 700 (fraction D). Fraction A was inactivated by trypsin digestion or by being heated at 56 degrees C for 2 h, suggesting that this factor might be a protein. The stimulating activity in fractions B, C, and D was dose-dependent. These stimulatory factors seemed to be different from known hormones such as insulin and glucagon.
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PMID:Characterization of liver regeneration stimulatory factor in human portal serum. 342 Dec 21

There is increasing evidence that factors derived from the seminiferous tubules influence Leydig cell function in a paracrine way. In previous experiments we demonstrated that conditioned media from Sertoli cell-enriched cultures contain a protein with stimulatory activity on prepubertal rat Leydig cells. In this paper we further studied the specificity of this factor. In addition we describe a simple but efficient partial purification procedure. It is demonstrated that Sertoli cell conditioned media contain a factor that stimulates the testosterone output from prepubertal and adult Leydig cells. The effects are evident within the first hour of incubation and can be observed in the presence as well as in the absence of LH. Peritubular cells do not produce a similar factor but enhance the production of the Leydig cell stimulating factor when cocultured with Sertoli cells. The Sertoli cell factor acts on rat as well as on mouse Leydig cells. It barely influences the adrenostenedione output of ovarian stromal cells or the corticosterone output of adrenal cells. The production of this factor is enhanced by dbcAMP, FSH, L-isoproterenol and glucagon but is not affected by androgens. The characteristics of the Sertoli cell factor have been compared with those of a Leydig cell stimulating factor in the medium from an established rabbit kidney cell line: RK13. It is shown that the active principle in RK13 conditioned medium is also a thermolabile trypsin-sensitive protein with a mol. wt of more than 10,000. Nonetheless, the RK13 and Sertoli cell derived factors act by different mechanisms since at maximally effective concentrations their effects are additive. Finally it is demonstrated that molecular weight fractionation of Sertoli cell conditioned medium using an Amicon ultrafiltration system results in a 50- to 130-fold increase in Sertoli cell factor activity in a fraction corresponding to a mol. wt of 10,000 up to 30,000.
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PMID:Specificity and partial purification of a factor in spent media from Sertoli cell-enriched cultures that stimulates steroidogenesis in Leydig cells. 353 64

Addition of insulin to isolated rat hepatocytes prelabeled with [32P]phosphate inhibited glucagon-dependent phospholipid methyltransferase phosphorylation and activation. Insulin alone had no effect on either the phosphorylation of the enzyme or on its activity. The effect of insulin on glucagon-dependent phospholipid methyltransferase phosphorylation was dose-dependent and occurred at physiological doses of the hormone (10(-11)-10(-10) M). Analysis of 32P-labeled peptides after digestion with trypsin revealed only one site of phosphorylation regulated by glucagon (10(-8) M) in isolated rat hepatocytes. This site, as analyzed by HPLC and thin-layer chromatography, coincided with that phosphorylated by the cAMP-dependent protein kinase using purified rat liver phospholipid methyltransferase.
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PMID:Inhibition by insulin of glucagon-dependent phospholipid methyltransferase phosphorylation in rat hepatocytes. 354 31

Three peptides isolated from the Brockmann bodies of the daddy sculpin, a teleostean fish, have been identified as fragments of one or more proglucagons. The peptide L Q D A E D S S R F D A D D T L A G E A R E L S T P K represents the NH2 terminus of proglucagon (residues 1-27), H S E G T F S N D Y S K Y L E T R R A Q D F V Q W L K N S represents glucagon and H A D G T F T S D V S S Y L N D Q A I K D F V A K L K S G K V represents the glucagon-like peptide at the COOH terminus of the precursor. The fast-atom bombardment mass spectra of the three peptides were consistent with the proposed structures and demonstrated that further posttranslational modifications of the peptides had not taken place. Sculpin glucagon is identical to anglerfish glucagon II but sculpin proglucagon(1-27) and glucagon-like peptide show stronger homology to the corresponding regions of anglerfish proglucagon I than to proglucagon II. The structures of the peptides are suggestive of the action of trypsin-like and carboxypeptidase-B-like enzymes at the site of pairs of basic amino acid residues in proglucagon. The presence of a COOH-terminal lysyl group in proglucagon(1-27) may indicate, however, that the penultimate prolyl residue partially inhibits the action of the carboxypeptidase-B-like activity.
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PMID:Primary structures of three fragments of proglucagon from the pancreatic islets of the daddy Sculpin (Cottus scorpius). 354 98

Protein carboxyl methyltransferases from erythrocytes and brain appear to catalyze the esterification of L-isoaspartyl and/or D-aspartyl residues but not of normal L-aspartyl residues. In order to identify the origin of these unusual residues which occur in subpopulations of a variety of cellular proteins, we studied the in vitro methylation by the erythrocyte enzyme of glucagon, a peptide hormone of 29 amino acids containing 3 aspartyl residues and a single asparagine residue. Methylated glucagon was digested with either trypsin, chymotrypsin, pepsin, or endoproteinase Arg C, and the labeled fragments were separated by high-performance liquid chromatography and identified. In separate experiments, methyl acceptor sites were determined by digesting glucagon first with proteases and then assaying purified glucagon fragments for methyl acceptor activity. Using both approaches, we found that the major site of methylation, accounting for about 62% of the total, was at the position of Asp-9. Chemical analysis of fragments containing this residue indicated that this site represents an L-isoaspartyl residue. A second site of methylation, representing about 23% of the total, was detected at the position of Asn-28 and was also shown to represent an L-isoaspartyl residue. Methyl acceptor sites were not detected at the positions of Asp-15 or Asp-21. Preincubation of glucagon under basic conditions (0.1 M NH4OH, 3 h, 37 degrees C) increased methylation at the Asn-28 site by 4-8-fold while methylation at the Asp-9 site remained unchanged. These results suggest that methylation sites can originate from both aspartyl and asparaginyl residues and that these sites may be distinguished by the effect of base treatment.
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PMID:Methylation at specific altered aspartyl and asparaginyl residues in glucagon by the erythrocyte protein carboxyl methyltransferase. 359 86

The binding of [14,15-3H]14,15-dihydroforskolin ([3H]DHF) to rat liver membranes has been further characterized and was compared with the stimulatory effect of forskolin on adenylate cyclase. The binding equilibrium dissociation constant (KD) for 14,15-dihydroforskolin obtained in inhibition experiments was 0.6 microM, with a maximal binding capacity (Bmax) of 114 pmol/mg protein. A similar KD value (0.5 microM) was derived from kinetics studies that revealed very rapid association and dissociation reactions. For structure-activity relationship studies several forskolin derivatives were synthesized and tested for their ability to inhibit [3H]DHF binding and increase adenylate cyclase activity. Among the tested compounds, forskolin itself was the most potent agonist (K1 = 0.2 microM). Further modification of the molecule in position 7 and (or) 1 decreased or abolished its agonist properties in both adenylate cyclase and binding studies. [3H]DHF binding was not affected by several nucleotides, carbohydrates, lectins, and hormone receptor agonists including isoproterenol, glucagon, and adenosine, but the steroids 17-beta-estradiol, progesterone, and testosterone showed slight inhibitory effects at unphysiologically high concentrations. [3H]DHF binding and forskolin-stimulated adenylate cyclase were sensitive to heat and N-ethylmaleimide treatment. Forskolin protected adenylate cyclase against inactivation by heat but not by N-ethylmaleimide. Preincubation of the membrane with trypsin decreased [3H]DHF binding. The results presented in this study demonstrate that the binding sites identified with [3H]DHF have a high specificity for forskolin and provide evidence that these binding sites are involved in the stimulation of adenylate cyclase by forskolin.
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PMID:Binding of [14,15-3H]14,15-dihydroforskolin to rat liver membranes: comparison with the stimulatory effect of forskolin on adenylate cyclase. 362 Oct 43

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.
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PMID:Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases. 381 76

Microcirculatory derangements in the pancreas associated with acute pancreatitis may contribute to a low-flow state and lead to pancreatic necrosis. This study investigated the effects of glucagon, a selective mesenteric arterial dilator, on pancreatic ischemia in canine bile-trypsin-induced pancreatitis (BTP). Measurements of cardiac Index (CI), total pancreatic blood flow (QP), pancreatic oxygen consumption (O2CP), and pancreatic arteriovenous shunt flow (QAVS) were obtained prior to and after inducing BTP. Bile-trypsin-induced pancreatitis was induced in 18 dogs. Nine received lactated Ringer's solution alone (LRPAN) at 6.5 mL/kg/hr, nine received lactated Ringer's solution plus continuous Intravenous (IV) glucagon hydrochloride (GLUPAN) at 1.0 micrograms/kg/min, and nine undergoing periportal dissection without BTP received IV glucagon (GLUCON). Following BTP, CI, QP, and O2CP decreased significantly and QAVS remained unchanged in crystalloid-treated animals (LRPAN). Glucagon administration (GLUPAN) transiently increased CI and QP but failed to improve O2CP and did not change QAVS. The decrease in O2CP observed after BTP in association with a constant QAVS suggests a metabolic block to oxygen uptake at the cellular level. Glucagon in pharmacologic doses does not reverse abnormalities in O2CP and is therefore of questionable physiologic benefit in the treatment of acute pancreatitis.
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PMID:Efficacy of pharmacologic glucagon in acute experimental pancreatitis. 397 Jun 71

Halothane, in a number of tissues, alters the activity of adenylate cyclase, the enzyme that catalyzes the formation of cyclic 3',5'-adenosine monophosphate, an important intracellular regulator. The present studies demonstrate that in rat liver whole homogenates, basal and glucagon-stimulated adenylate cyclase activity is increased by halothane. In isolated rat liver membranes, halothane does not increase basal activity and it decreases activity stimulated by glucagon. Suspension of membranes in the cytosol fraction restores the halothane-induced increase of basal and glucagon-stimulated activity. When cytosol denatured by trypsin or heat was used, the halothane-induced increase in glucagon-stimulated activity was lost, but the increase of basal activity was still observed. Suspension of membranes in albumin solution restored the effect of halothane on basal activity only. These results suggest that presence of heat-labile proteins in the cytosol fraction that modulate the halothane interaction with rat liver adenylate cyclase.
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PMID:Effect of halothane on rat liver adenylate cyclase: role of cytosol components. 399 14


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