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)

Glucagon and glucagon-(1-21)-peptide were equipotent with regard to inhibitory effect on the amplitude of electrically evoked contractions of the isolated guinea-pig ileum. The effect was not potentiated by isobutylmethylxanthine (IBMX) nor inhibited by phentolamine or propranolol. Both peptides inhibited intestinal motility in rabbits in vivo. Glucagon and equimolar doses of glucagon-(1-21)-peptide exerted a relaxing effect on the rabbit gall bladder in vitro and in vivo and increased bile flow in rats. Both peptides inhibited pentagastrin stimulated gastric acid secretion in cats. However, contrary to glucagon, glucagon-(1-21)-peptide did not increase blood glucose and plasma IRI levels after intravenous administration to rats in vivo. Whereas the entire glucagon molecule was required for the metabolic effects, the amino acid sequence (1-21) of glucagon exerted a full spasmolytic action on the enteric muscles and the biliary tree. The spasmolytic effects on these organs are therefore likely to be mediated via a mechanism that does not involve the activation of adenyl cyclase.
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PMID:Dissociation of the spasmolytic and metabolic effects of glucagon. 657 8

Hepatocytes, endothelial and Kupffer cells were isolated from young adult (3 month) and old (24 month) rat livers and the activities of some plasma membrane, endoplasmic reticulum, mitochondrial, lysosomal and soluble enzymes compared using biochemical and electron microscope cytochemical techniques. Age-associated changes included: a decrease in glucose-6-phosphatase activity both in hepatocytes and sinus lining cells; and increase in alkaline phosphatase in endothelial cells but a decrease in hepatocytes; reduced basal and glucagon-induced adenyl cyclase in hepatocytes and endothelial cells and an increase in the number of hepatocytes with gamma-glutamyl transferase reaction. Cytochemistry showed that heterogeneity may also be characteristic of senescence particularly with regard to hepatocyte glucose-6-phosphatase which was absent in some cells, low in many cells but high in some and gamma-glutamyl transferase which was normally lacking from hepatocytes but localised as large deposits of reaction product on the plasma membranes of occasional cells isolated from old donors.
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PMID:Effects of age on rat liver enzymes. A study using isolated hepatocytes, endothelial and Kupffer cells. 706 Sep 52

The trinitrophenyl (TNP) derivative of glucagon has less lipolytic activity and potency than the carbamyl derivative. The N alpha, e-acetyl derivative has slightly less activity than the TNP derivative. In contrast to liver, where the TNP derivative fails to stimulate adenyl cyclase, all the derivatives stimulate this enzyme in the adipocyte.
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PMID:Lipolytic and adenyl-cyclase-stimulating activity of N alpha-trinitrophenyl glucagon: comparison with other glucagon derivatives modified at the amino terminus. 706 87

Adenylate cyclase [ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] was shown to be present in cultured human articular chondrocytes. Optimal conditions of incubation time, protein and substrate concentrations and pH were determined in whole cell lysates. Maximal activity occurred at pH 8.5 with no decrease in activity up to pH 10.0. Adenylate cyclase activity of particulate membrane preparations was enhanced by the addition of crude cytosol preparations. The prostaglandins E1, E2, F1 alpha, F2 alpha, D2, B1, B2, A1 and A2, as well as adrenaline and isoprenaline, stimulated adenylate cyclase derived from either adult or foetal chondrocytes. No significant stimulation was observed in the presence of human calcitonin or glucagon. Bovine parathyroid hormone always significantly stimulated the adenylate cyclase derived from foetal chondrocytes, but not from adult chondrocytes. Preincubation of the chondrocytes in culture with indomethacin and with or without supernatant medium from cultured mononuclear cells increased the responsiveness of the adenylate cyclase to prostaglandin E1.
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PMID:Adenylate cyclase of human articular chondrocytes. Responsiveness to prostaglandins and other hormones. 715 97

Glucagon 1-6 has a maximum lipolytic activity (Lmax) in the rat adipocyte which is 66% of that of glucagon. The N epsilon-guanidyl derivative, modified at Lys12, has about the same Lmax as glucagon 1-6. Modifying the carboxyl groups of glucagon with glycinamide or removing the COOH-terminal residues with cyanogen bromide reduces Lmax to less than 25% of the level of glucagon. The potency of each of these analogs (A50) in microM is as follows: glucagon 6 X 10(-3); glucagon 1-6 2 X 10(-2); N epsilon-guanidyl glucagon 9 X 10(-3); glycinamide glucagon 10(-2); cyanogen bromide peptide of glucagon 2 X 10(-1). The ability of all of the glucagon analogs to stimulate adenyl cyclase was somewhat less than their lipolytic activities with the exception of the glycinamide derivative and the cyanogen bromide peptide, which were slightly more active in stimulating adenyl cyclase than in lipolysis. Glucagon 1-6 is much more potent in stimulating adipocyte than liver adenyl cyclase.
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PMID:Lipolytic and adenyl-cyclase-stimulating activity of glucagon 1-6: comparison with glucagon derivatives chemically modified in the 7-29 sequence. 717 45

Molybdate activation of rat liver plasma membrane adenylate cyclase has been examined and compared with the effect of glucagon, Gpp(NH)p and fluoride. Glucagon does not stimulate the detergent solubilized enzyme though molybdate, fluoride, and Gpp(NH)p are effective in this regard. The stimulatory effects of either fluoride or molybdate are additive with those of GTP and do not require guanyl nucleotide to evoke their activation. Neither fluoride nor molybdate can substitute for GTP when glucagon is the activator of rat liver adenyl cyclase. The stimulatory effects of either ion on adenylate cyclase are additive with that produced by glucagon. Activation of adenylate cyclase by either molybdate or fluoride occurs by a mechanism distinct from that of glucagon or guanyl nucleotide. The data presented her suggest that fluoride and molybdate may act via in a similar mechanism of action. Neither ion displays a lag in activation of adenylate cyclase. The pH profiles of fluoride and molybdate-stimulated adenylate cyclase activity are similar, and distinct from guanyl nucleotide-stimulated activity. Cholera toxin treatment of adenylate cyclase blocks fluoride and molybdate stimulation of the enzyme to the same extent, while enhancing the activation obtained with GTP and hormones.
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PMID:Mechanism of molybdate activation of adenylate cyclase. 731 47

The cellular mechanisms associated with the replicative response of hepatocytes to growth factor simulation is incompletely understood. Murine hepatocyte DNA synthesis is altered by cyclic AMP, suggesting that protein kinase A is involved in the cellular mechanisms associated with liver growth. The purpose of this study was to evaluate the role of protein kinase A in human hepatocyte DNA synthesis. human hepatocytes were isolated and maintained in primary culture on rat tail collagen. DNA synthesis was evaluated by determining [3H] thymidine incorporation. Human hepatocytes between 24 and 96 hr following harvest increased DNA synthesis in response to epidermal growth factor but not in response to glucagon, a stimulant of adenyl cyclase, or dibutyryl cyclic AMP. Mitogen-stimulated DNA synthesis was decreased by dibutyryl cyclic AMP. Cyclic AMP isomers that block or stimulate the effect of cyclic AMP on protein kinase A did not significantly alter resting or mitogens-stimulated human hepatocyte DNA synthesis. The results suggest that increased protein kinase A activity does not produce human hepatocyte replicative DNA synthesis.
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PMID:Role of protein kinase A in human hepatocyte DNA synthesis. 862 44

We have designed and synthesized eight compounds 2-9 which incorporate neutral, hydrophobic amino acid residues in positions 9, 11 and 16 of the glucagon molecule: (2) [desHis1, Val9. Ile11,16] glucagon amide, (3) [desHis1, Val9,11,16] glucagon amide, (4) [desHis1, Val9, Leu11,16]glucagon amide, (5) [desHis1, Nle9, Ile11,16]glucagon amide, (6) [desHis1, Nle9, Val11,16] glucagon amide, (7) [desHis1,-Nle9, Leu11,16] glucagon amide, (8) [desHis1, Val9, Leu11,16, Lys17,18, Glu21] glucagon amide and (9) [desHis1, Nle9, Leu11,16, Lys17,18, Glu21] glucagon amide. The effect of neutral, hydrophobic residues at positions 9, 11 and 16 led to good binding to the glucagon receptor. Compared to glucagon (IC50 = 1.5 nM), analogues 2-9 were found to have IC50 values of 6.0, 6.0, 11.0, 9.0, 2.5, 2.8, 6.5 and 7.0 nM, respectively. When these compounds were tested for their ability to block adenylate cyclase (AC) activity, they were found to be antagonists having no stimulation of adenyl cyclase, with pA2 values of 6.15, 6.20, 6.30, 7.25, 6.10, 7.30, 6.25 and 7.25, respectively.
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PMID:Structure-activity studies of hydrophobic amino acid replacements at positions 9, 11 and 16 of glucagon. 917 12

Glucagon-like peptide 1 (GLP-1), a hormonal activator of adenyl cyclase, stimulates insulin gene transcription, an effect mediated by the cAMP response element (CRE) of the rat insulin I gene promoter (RIP1). Here we demonstrate that the signaling mechanism underlying stimulatory effects of GLP-1 on insulin gene transcription results from protein kinase A (PKA)-independent activation of the RIP1 CRE. Although GLP-1 stimulates cAMP production in rat INS-1 insulinoma cells, we find accompanying activation of a -410-bp RIP1 luciferase construct (-410RIP1-LUC) to exist independently of this second messenger. GLP-1 produced a dose-dependent stimulation of -410RIP1-LUC (EC50 0.43 nmol/l), an effect reproduced by the GLP-1 receptor agonist exendin-4 and abolished by the antagonist exendin(9-39). Activation of RIP1 by GLP-1 was not affected by cotransfection with dominant-negative Gs alpha, was not blocked by cAMP antagonist Rp-cAMPS, and was insensitive to PKA antagonist H-89. Truncation of -410RIP1-LUC to generate -307-, -206-, and -166-bp constructs revealed 2 segments of RIP1 targeted by GLP-1. The first segment, not regulated by forskolin, was located between -410 and -307 bp of the promoter. The second segment, regulated by both GLP-1 and forskolin, included the CRE and was located between -206 and -166 bp. Consistent with these observations, stimulatory effects of GLP-1 at RIP1 were reduced after introduction of delta-182 and delta-183/180 inactivating deletions at the CRE. The action of GLP-1 at -410RIP1-LUC was also reduced by cotransfection with A-CREB, a genetically engineered isoform of the CRE binding protein CREB, which dimerizes with and prevents binding of basic-region-leucine-zipper (bZIP) transcription factors to the CRE. In contrast, the action of GLP-1 at the CRE was not blocked by cotransfection with M1-CREB, an isoform that lacks a consensus serine residue serving as substrate for PKA-mediated phosphorylation. On the basis of these studies, it is proposed that PKA-independent stimulatory actions of GLP-1 at RIP1 are mediated by bZIP transcription factors related in structure but not identical to CREB.
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PMID:Glucagon-like peptide 1 stimulates insulin gene promoter activity by protein kinase A-independent activation of the rat insulin I gene cAMP response element. 1090 73

The peptide synthesised by us: 387-394-amide (10(-7)-10(-4) M), in a dose dependent manner decreases activities of adenyl cyclase and proteinkinase A evoked by serotonine and glucagon in smooth muscles of the freshwater bivalve mollusc Anodonta cygnea and that evoked by beta-agonist isoproterenol--in the rat skeletal muscles. Even in concentration 10(-7) M, the peptide completely eliminates potentiation of the hormones' stimulating effect on adenylyl cyclase activity with the non-hydrolizable analogue of guanine nucleotides (Gpp[NH]p). At the same time, the peptide does not affect stimulation of the adenylyl cyclase activity with non-hormonal agents (NaF, Gpp[NH]p and forkolin). In the presence of the peptide, inhibiting effects of the hormones on activities of adenylyl cyclase and protein kinase A will be preserved. The findings reveal the importance of the G-protein alpha s-subunit's C-terminal regional of a stimulating type for its functional coupling with receptors of a serpentine type, and elucidate the molecular mechanisms of interaction between the G-protein and the receptor.
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PMID:[Effect of C-terminal peptide of G-protein alfa(s)-subunit on regulation of adenylate cyclase and protein kinase A activities by biogenic amines and glucagon in mollusc and rat muscles]. 1475 20


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